We read with interest the paper of M Sebastianni et al about the predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis(1). The authors suggest that the CSURI score "can represent a feasible and reliable clinical tool in the routine evaluation of patients". However, we feel this report raises serious issues concerning the reproducibility of the methodology. When calculating the score, the num...
We read with interest the paper of M Sebastianni et al about the predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis(1). The authors suggest that the CSURI score "can represent a feasible and reliable clinical tool in the routine evaluation of patients". However, we feel this report raises serious issues concerning the reproducibility of the methodology. When calculating the score, the number of capillaries ("N") was the most important predictive index. The definition of the "N" is clearly detailed and the clinicians have to count "all the capillaries detectable in the entire distal front line, including capillaries placed at different levels". The measurement was illustrated in figure 1 and we noticed that that the author were counting 13 capillaries on the panel C as specified in the legend.
However, the same picture was used 3 years ago, when the same authors described the score(2), excepted that the picture was a little larger and included one more capillary on the right of the picture, and the authors counted only 11 capillaries. We were surprised about such a huge difference in capillary counting, especially in didactic pictures which have the aim to illustrate the methodology of the score.
This difference may be induced by the difficulty of defining the "entire distal front line". It also reflects the difficulty of capillary counting using native videocapilaroscopy that could be overcome by using fluorescent dyes. It is difficult to estimate the extrapolation of this error on the score MxD/N2 but, it seems clear that the reproducibility of the CSURI remains questionable. Although the aim to build-up an informative and easy to use capillaroscopic score is a highly valuable purpose, the reproducibility of such measurements remains a stumbling stone difficult to get round.
References
1. Sebastianni M, Manfredi A, Vukatana G, et al. Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study. Ann Rheum Dis 2012;71:67-70.
2. Sebastiani M, Manfredi A, Colaci M, et al. Capillaroscopic skin ulcer risk index: a
new prognostic tool for digital skin ulcer development in systemic sclerosis patients. Arthritis Rheum 2009;61:688-94.
Osteoarthritis can occur at almost any joint, osteoarthritis of the
knee is the most common type. More than 10 million Americans have
osteoarthritis of the knee. Most people affected are older than 45 years.[1]
The published article by K L Bennel et al. lacks patient’s information
like patient’s age, sex, weights, heights, and family history. In this
article K L Bennel et al. concluded that p...
Osteoarthritis can occur at almost any joint, osteoarthritis of the
knee is the most common type. More than 10 million Americans have
osteoarthritis of the knee. Most people affected are older than 45 years.[1]
The published article by K L Bennel et al. lacks patient’s information
like patient’s age, sex, weights, heights, and family history. In this
article K L Bennel et al. concluded that physiotherapy trial was no more
effective than regular contact with a therapist at reducing pain and
disability. Osteoarthritis is a Multifactorial disease. Many factors
influence patient’s morbidity. Many studies had been done to see the
efficacy of treatment options in osteoarthritis of joints. Most of the
study reports really put us in a questionable position.
An article[2] “efficacy of acupuncture on osteoarthritic pain”
published in NEJM. The experimental group received treatment at standard
acupuncture points, and the control group at placebo points. Gaw A. C at
el in this study found that Thus, both experimental and control groups
showed a reduction in pain after the treatments. These results may reflect
the natural course of illness, and various attitudinal and social factors.
Many patients report symptomatic relief after undergoing arthroscopy
of the knee for osteoarthritis, but it is unclear how the procedure
achieves this result. Efficacy of arthroscopic surgery for osteoarthritis
treatment is also confusing. In a study[3] by J. Bruce Moseley et al. did
randomized, placebo-controlled trial to evaluate the efficacy of
arthroscopy for osteoarthritis of the knee. The outcomes after
arthroscopic lavage or arthroscopic débridement were no better than those
after a placebo procedure.
Even intra-articular hyaluronan injections have little benefit for
osteoarthritis (OA) of the knee and that the effect is similar in
magnitude to the superiority of nonsteroidal anti-inflammatory drugs
(NSAIDs) over acetaminophen.[4]
Dr Lo and colleagues1 concluded that intra-articular hyaluronan
injections have little benefit for osteoarthritis (OA) of the knee and
that the effect is similar in magnitude to the superiority of nonsteroidal
anti-inflammatory drugs (NSAIDs) over acetaminophen.
Aerobic exercise and resistance exercise showed a promising step in
osteoarthritis patients. In a study[5] W. H. Ettinger Jr et al. found that
Older disabled persons with osteoarthritis of the knee had modest
improvements in measures of disability, physical performance, and pain
from participating in either an aerobic or a resistance exercise program.
Their data suggest that exercise should be prescribed as part of the
treatment for knee osteoarthritis.
Reference:
1. Sharon Parmet; Cassio Lynm; Richard M. Glass
Osteoarthritis of the Knee. JAMA, Feb 2003; 289: 1068.
2. Efficacy of acupuncture on osteoarthritic pain. A controlled,
double-blind study. Gaw A. C., Chang L. W., Shaw L-C . N Engl J Med 1975; 293:375-378, Aug 21,
1975.
3. A Controlled Trial of Arthroscopic surgery for osteoarthritis of
the knee. Moseley J. B., O'Malley K., Petersen N. J., Menke T. J., Brody B. A.,
Kuykendall D. H., Hollingsworth J. C., Ashton C. M., Wray N. P. N Engl J
Med 2002; 347:81-88, Jul 11, 2002.
4. Grace H. Lo; David Felson; Michael LaValley
Intra-articular Hyaluronic Acid for Treatment of Osteoarthritis of the
Knee. JAMA, March 24/31, 2004; 291: 1441-1442.
5. W. H. Ettinger Jr; R. Burns; S. P. Messier; W. Applegate; W. J.
Rejeski; T. Morgan; S. Shumaker; M. J. Berry; M. O'Toole; J. Monu; T.
Craven. A randomized trial comparing aerobic exercise and resistance exercise with
a health education program in older adults with knee osteoarthritis. The
Fitness Arthritis and Seniors Trial (FAST). JAMA, Jan 1997; 277: 25-31.
We have read the reply from the authors to our letter. As a final
remark we would like to repeat our previous statement: “From a clinician’s
perspective we think that health economic analyses in RA should always be
done with intimate knowledge of the patient cohort on which the
calculations are based. Any projection and modelling in other settings
must be carried out with great care in close collabora...
We have read the reply from the authors to our letter. As a final
remark we would like to repeat our previous statement: “From a clinician’s
perspective we think that health economic analyses in RA should always be
done with intimate knowledge of the patient cohort on which the
calculations are based. Any projection and modelling in other settings
must be carried out with great care in close collaboration between
scientists trained in health economics and rheumatologists”. Such
collaboration would have modified several of the statements made in the
article.
Pierre Geborek, MD, PhD
Tore Saxne, Professor
Dept of Rheumatology
Lund University Hospital
SE-221 85 Lund, Sweden Pierre.geborek@reum.lu.se
We read with interest the recent article “Smoking is a risk factor
for anti-CCP antibodies only in RA patients that carry HLA-DRB1 Shared
Epitope alleles” by Dr. Linn-Rasker and colleagues in Leiden.[1] The
question of whether true gene-environment interaction exists between
genotype (HLA-DRB1 shared epitope, SE) and an environmental exposure,
cigarette smoking in this case, both of which are known to...
We read with interest the recent article “Smoking is a risk factor
for anti-CCP antibodies only in RA patients that carry HLA-DRB1 Shared
Epitope alleles” by Dr. Linn-Rasker and colleagues in Leiden.[1] The
question of whether true gene-environment interaction exists between
genotype (HLA-DRB1 shared epitope, SE) and an environmental exposure,
cigarette smoking in this case, both of which are known to greatly
increase the risk of developing RA, is central to our understanding of how
these factors predispose to RA. Does the risk associated with having both
of these risk factors exceed what would be expected if these risks were
independent and additive, and how so? Case-only analyses, such as this,
are an efficient and sound method for screening for gene-environment
interactions, under the assumption of independence of exposure and
genotype in the population.[2,3]
In a recent editorial, Ahlbom and Alfredsson explained the concepts
of biological versus statistical interaction.[4,5] Biological
interaction is seen when two risk factors are involved in the same pathway
to development of disease; statistically this is seen as a departure from
additivity of disease rates. For example, Padyukov and colleagues in
Sweden have demonstrated that a greater than additive interaction exists
for the effects of cigarette smoking and the presence of 0, 1 or 2 copies
of the SE.[6] To do so, they calculated the attributable proportion (AP),
the proportion of RA among those with both exposures that is attributable
to an additive interaction between these risk factors.[7] They found that
among current smokers with a double copy of the SE, the AP is 0.7, or 70%,
(95% CI 0.4, 0.9).[6] Another way of statistically testing for gene-environment interaction is to create a cross-classified variable, or
interaction term, in a logistic regression model, and test it for
significance, pointing to a greater than multiplicative interaction that
is significant.
In their study, Linn-Rasker and colleagues employed a case-only
analysis of patients in the Leiden Early RA clinic to evaluate the
interaction between smoking and HLA-SE in predicting the risk of Anti-CCP
antibodies. Their findings are very interesting and suggest an interaction
between the two exposures, but it does not appear that the presence of a
gene-environment interaction was statistically tested. We have employed
their data to test statistically for the presence of a gene-environment
interaction, both greater than additive and greater than multiplicative.
Using the data presented in table 2 of their article, the AP, or the
proportion of RA cases positive for anti-CCP antibodies which is
attributable to an interaction between cigarette smoking and the presence
of the SE, is 0.5, or 50%. (Given our limited access to the data, we are
not able to use a re-sampling technique to obtain a 95% confidence
interval.) When a cross-classified variable (smoking x HLA-SE) is created
and employed in a logistic regression model using the data in Table 2, the
term is not significant for a multiplicative interaction (p=0.19).
Employing the terminology suggested by Ahlbom and Alfredsson,[4,5] the
fact that an additive, but not multiplicative, interaction exists is
important and suggests that cigarette smoking and HLA SE lie on the same
causal pathway to the development of anti-CCP antibodies and RA.
Presenting such statistical analyses promotes translational research
between epidemiologists and basic scientists.
Karen H. Costenbader, MD, MPH (A)
Lori B. Chibnik, MPH (A)
Lisa Mandl, MD, MPH (B)
Elizabeth W. Karlson, MD (A)
(A) Brigham and Women’s Hospital, Harvard Medical School, Boston,
MA
(B) Hospital for Special Surgery, Weill Cornell Medical College, New York,
NY
References
1. Linn-Rasker SP, van der Helm-van Mil AH, Van Gaalen FA,
Kloppenburg M, de Vries R, le Cessie S, Breedveld FC, Toes RE, Huizinga
TW. Smoking is a risk factor for anti-CCP antibodies only in RA patients
that carry HLA-DRB1 Shared Epitope alleles. Ann Rheum Dis 2005.
2. Botto LD, Khoury MJ. Commentary: facing the challenge of gene-
environment interaction: the two-by-four table and beyond. Am J Epidemiol
2001; 153:1016-20.
3. Gatto NM, Campbell UB, Rundle AG, Ahsan H. Further development of the
case-only design for assessing gene-environment interaction: evaluation of
and adjustment for bias. Int J Epidemiol 2004; 33:1014-24.
4.
Andersson T, Alfredsson L, Kallberg H, Zdravkovic S, Ahlbom A.
Calculating measures of biological interaction. Eur J Epidemiol 2005;
20:575-9.
5. Ahlbom A, Alfredsson L. Interaction: A word with two meanings creates
confusion. Eur J Epidemiol 2005; 20:563-4.
6. Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. A gene-
environment interaction between smoking and shared epitope genes in HLA-DR
provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum
2004; 50:3085-92.
7. Rothman KJ, Greenland S, Walker AM. Concepts of interaction. Am J
Epidemiol 1980; 112:467-70.
We read the study by Saraux et al (1) on the prevalence of
Spondyloathropaties (SpA)s in France with great interest. In this well
designed study, 9395 subjects were interviewed over the phone using a
structured questionnaire. SpA was confirmed in 29 patients by the
patient’s rheumatologist or by clinical examination. Of these 29 patients,
13 had ankylosing spondylitis (AS) and 11 had psoriatic arthri...
We read the study by Saraux et al (1) on the prevalence of
Spondyloathropaties (SpA)s in France with great interest. In this well
designed study, 9395 subjects were interviewed over the phone using a
structured questionnaire. SpA was confirmed in 29 patients by the
patient’s rheumatologist or by clinical examination. Of these 29 patients,
13 had ankylosing spondylitis (AS) and 11 had psoriatic arthritis (PsA)
who were diagnosed clinically by the patients’ rheumatologist
independently from any classification criteria. One additional patient
had been given two diagnoses, AS and PsA; undifferentiated SpA (uSpA) was
established in the remaining 4 patients. Although, at least 45% (13/29) of
the SpA patients were identified to have AS, standardized prevalence rate
of AS (0.08%) reported in the study was only 27% of that of SpA (0.30%).
Moreover, despite the fact that the number of cases with AS (n=13)
slightly exceeded that of PsA (n=11), standardized prevalence rate of
AS was less than half of that found for PsA (0.08% vs. 0.19%,
respectively).
Thus, we have taken the challenge to recalculate the
figures reported by the authors using the age and sex distributions of the
patients with different diagnostic categories, which we extracted from
the authors’ original article (1) and the age and sex distributions of
the sample and source populations which was provided in a companion
article(2). We included the patient who had received two diagnoses, AS
and PsA, in the PsA group. It was not clear how the authors considered
this patient when computing their estimates; but because they stated in
the results section that AS was diagnosed in 14 patients and PsA in 12
patients, they might have included her in both groups. We used StatsDirect
statistical software (version 2.5.2) for calculating the standardized
prevalence rates and improved approximate (Dobson) 95% confidence
intervals. We found the same prevalence rate for SpA to that obtained by
the authors; but, quite different prevalence rates for AS (0.14%, (95%CI
0.07 to 0.24)) and PsA (0.012%, (95%CI 0.06 to 0.22)) than were reported
by them (0.08% and 0.19%, respectively). Although, not given in the
original article, we also calculated the prevalence of AS in different
sexes and found that prevalence rate of AS in males (0.16%, (95%CI 0.06
to 0.35)) was only slightly higher than that found in females (0.11%,
(95%CI 0.05 to 0.24)) suggesting the better appreciation of AS in
females in the recent years.
We wonder whether the authors will agree with these figures.
References
1. Saraux A, Guillemin F, Guggenbuhl P, Roux CH, Fardellone P, Le
Bihan E, et al. Prevalence of spondyloarthropathies in France: 2001. Ann
Rheum Dis 2005; 64: 1431-5.
2. Guillemin F, Saraux A, Guggenbuhl P, Roux CH, Fardellone P, Le
Bihan E, et al. Prevalence of rheumatoid arthritis in France: 2001. Ann
Rheum Dis 2005; 64: 1427-30.
We found the study by Elkayam et al (1) of great interest, as it
sheds more light on the complex scenario of anti cyclic citrullinated
peptide antibodies (anti-CCP), originally described as highly specific for
rheumatoid arthritis (RA). Indeed, it appears that an immune response to
these proteins is initiated (though it’s not yet clear how sustained) in
several other conditions. It is not surprising t...
We found the study by Elkayam et al (1) of great interest, as it
sheds more light on the complex scenario of anti cyclic citrullinated
peptide antibodies (anti-CCP), originally described as highly specific for
rheumatoid arthritis (RA). Indeed, it appears that an immune response to
these proteins is initiated (though it’s not yet clear how sustained) in
several other conditions. It is not surprising that tuberculosis (TB) and
RA may share serological markers like rheumatoid factor and, now, anti-
CCP. The cytokine profile of these inflammatory diseases is, in fact,
largely overlapping: type 1 cytokines and TNF-α are important in the
defense against mycobacteria infection and pathogenesis of TB granuloma as
well as in the induction and maintainance of RA synovial inflammation. The
association of anti-CCP with other rheumatological and autoimmune diseases
is less granted, but it’s being reported increasingly (2, 3).
We ourselves
have evaluated the occurrence of anti-CCP in 483 sera of patients with
rhematological (psoriatic and reactive arthritis, primary and erosive
osteoarthritis) and autoimmune diseases (connective tissue diseases,
autoimmune liver disease, celiac disease). Anti-CCP were tested using the
commercial ELISA kit Diastat (Axis-Shield, Dundee, Scotland, UK) with sera
diluted 1:100, according to the manufacturer’s instructions. They were
globally detected in 76 sera (16%). The highest prevalence was found, as
expected, in RA (53 out of 89, 60%). As also expected, the antibodies were
found in a proportion of patients with psoriatic arthritis (2 out of 23,
9%), but they were positive also in erosive osteoarthritis (2/35, 5%),
connective tissue diseases (4/42, 9%) and, especially, in autoimmune liver
diseases (autoimmune hepatitis and primary biliary cirrhosis), in which we
found 14 positive cases out of 182 (8%) (4). As in TB (1), no correlation
was found between anti-CCP seropositivity and symptoms or signs of
arthritis in autoimmune cases. High titres (≥ 20 with the ELISA kit
used in our laboratory) were present in 75% RA positive sera, but also in
62% positive sera from non-RA patients. Anti-CCP, as detected by this
commercially available ELISA, do not seem to be entirely specific for RA
and the results of this test should be critically evaluated in the
clinical setting. This consideration holds particularly true for overlap
syndromes or in early RA, where anti-CCP have been included in prediction
models used to select patients for more aggressive therapeutic approach
(5).
In fact, in a recent study, by Gao et al (6) it’s been established
that the positive predictive value of anti-CCP alone (the probability of
fulfilling the ACR criteria for RA) was of little help to accurately
predict RA. As the exact nature of the target antigen(s) used in the ELISA
kit is still unknown, it’s entirely possible that non-RA-associated anti-
CCP do bind to citrullinated proteins, that are different from those
recognized by RA sera. If future studies will better characterize the
nature of the antigens involved in the different anti-CCP associated
diseases and when more specific tests will be set up, only then anti-CCP
will deserve a unique place in the diagnosis and management of RA.
Reference
1. Elkayam O, Segal R, Lidgi M, Caspi D. Positive anti-cyclic
citrullinated proteins and rheumatoid factor during active lung
tubercolosis. Ann Rheum Dis 2005 Dec 16; (Epub ahead of print).
2. Hoffman IE, Peene I, Cebecauer L, Isenberg D, Huizinga TW, Union A et
al. Presence of rheumatoid factor and antibodies to citrullinated peptides
in systemic lupus erythematosus. Ann Rheum Dis. 2005;64:330-2.
3. Vander Cruyssen B, Hoffman IE, Zmierczak H, Van den Berghe M, Kruithof
E, De Rycke et al. Anti-citrullinated peptide antibodies may occur in
patients with psoriatic arthritis. Ann Rheum Dis. 2005;64:1145-9.
4. Fusconi M, Vannini A, Dall’Aglio AC, Pappas G, Cassani F, Ballardini G
et al. Anti-cyclic citrullinated peptide antibodies in type 1 autoimmune
hepatitis. Aliment Pharmacol Ther 2005;22:951-5.
5. Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JMW. How to diagnose
rheumatoid arthritis early: A prediction model for persistent (erosive)
arthritis. Arthritis Rheum 2002;46:557-65.
6. Gao IK, Haas-Wöhrle A, Mueller KG, Lorenz H-M, Fiehn C. Determination
of anti-CCP antibodies in patients with suspected rheumatoid arthritis:
does it help to predict the diagnosis before referral to a rheumatologist?
Ann Rheum Dis 2005;64:1516-7.
We read with great interest the recently published article by Otero et al. [1] where they report significantly increased levels of leptin, adiponectin and visfatin plasma levels in patients with rheumatoid arthritis compared with controls. Their finding concerning the level of leptin in rheumatoid arthritis contradicts the results from other studies including our own (Ljung et al, submitted).[2][3] Our co...
We read with great interest the recently published article by Otero et al. [1] where they report significantly increased levels of leptin, adiponectin and visfatin plasma levels in patients with rheumatoid arthritis compared with controls. Their finding concerning the level of leptin in rheumatoid arthritis contradicts the results from other studies including our own (Ljung et al, submitted).[2][3] Our concern in this matter is that the relation of male vs. female subjects differs in the patient group and the control group, with 71% females among the patients and only 56% females among controls.
It is well known that serum leptin levels are considerably higher in females than in males, and the mean
levels presented in females are more than double the levels in males. [4][5] The same goes for adiponectin, although not as dramatically different. [5] Thus, there is a risk that this influences the results. It is tempting to conclude, that the significance levels (p < 0.05) obtained in the statistical analyses of leptin and adiponectin reflect the
lack of gender stratification. We would be interested to see the groups divided by sex to appreciate the value of the results.
Lotta Ljung, MD Solbritt Rantapää Dahlqvist, MD, Professor.
Department of Public Health and Clinical Medicine, Rheumatology,
University Hospital, 901 85 Umeå, Sweden.
References
1 Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gomez-Reino JJ, et al.
Changes in fat-derived hormones plasma concentrations: adiponectin,
leptin, resistin, and visfatin in rheumatoid arthritis subjects. Ann Rheum
Dis 2006 Jan 13;[Epub ahead of print]
2 Popa C, Netea MG, Radstake TR, van Riel PL, Barrera P, van der Meer
JW. Markers of inflammation are negatively correlated with serum leptin in
rheumatoid arthritis. Ann Rheum Dis 2005;64:1195-8
3 Anders HJ, Rihl M, Heufelder A, Loch O, Schattenkirchner M. Leptin
serum levels are not correlated with disease activity in patients with
rheumatoid arthritis. Metabolism 1999 Jun;48:745-8.
4 Hickey MS, Israel RG, Gardiner SN, Considine RV, McCammon MR,
Tyndall GL, et al. Gender differences in serum leptin levels in humans.
Biochem Mol Med 1996;59:1-6.
5 Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, et
al. Relationship of adiponectin to body fat distribution, insulin
sensitivity and plasma lipoproteins: evidence for independent roles of age
and sex. Diabetologia 2003;46:459-69.
I read with interest the recent study describing clinical
characteristics associated with antibodies that bind fragments of the Mi-2
beta antigen1 and it raises the question of how to best define
autoantibodies. For economic reasons, ELISAs are taking over much of the
immunology testing in rheumatology practice today. ELISAs are being used
despite their often limited validation and the many concerns...
I read with interest the recent study describing clinical
characteristics associated with antibodies that bind fragments of the Mi-2
beta antigen1 and it raises the question of how to best define
autoantibodies. For economic reasons, ELISAs are taking over much of the
immunology testing in rheumatology practice today. ELISAs are being used
despite their often limited validation and the many concerns regarding the
sensitivity, specificity and reproducibility of these approaches.2 There
is considerable evidence that ELISA assays may not be measuring the same
antibody populations that have traditionally been detected by
immunodiffusion, indirect immunofluorescence or immunoprecipitation
methods – the classic approaches that originally defined the clinical
usefulness of most autoantibodies in systemic rheumatic conditions. Many
groups have recognized this problem, and coordinated efforts similar to
those of the Diabetes Antibody Standardisation Program to improve the
sensitivity, specificity and comparability of the measurement of
autoantibodies associated with type 1 diabetes
(http://www.idsoc.org/committees/antibody/dasphome.html) should be
encouraged in other fields.
Important examples in the literature also show that antibodies raised
against a given antigen may not interact with the target protein in the
same way that spontaneously occurring autoantibodies do, and it is
possible that such differences have important implications regarding the
origin and pathologic significance of human autoantibodies. Prime examples
are anti-Jo-1 autoantibodies directed against histidyl-tRNA synthetase.
These myositis-specific autoantibodies were originally defined by
immunodiffusion and immunoprecipitation of the target protein in a complex
with its cognate tRNA and were found in all cases to inhibit the function
of the target antigen.3 Later studies in mice suggested that antibodies
could easily be induced that bind histidyl-tRNA synthetase, however, they
were completely different in their disease association, epitope
specificity, capacity to immunoprecipitate the target antigen with its
cognate tRNA, and their ability to inhibit the function of the antigenic
enzyme.4 Should such different antibodies also be called anti-Jo-1
autoantibodies? I think not and suggest that they should rather be
referred to simply as antibodies that bind histidyl-tRNA synthetase or its
peptide fragments by the methodology used.
I believe that this issue is a widespread one and a clarification of
such antibody nomenclature would enhance our understanding and
appreciation of the limitations that different methodologies impose.
Until and unless data are generated to demonstrate that a new method of
measuring a particular autoantibody gives equivalent results to a
previously validated approach, I believe that it would be desirable that
the “new antibody” should be given a new name in conjunction with the
methodology used to detect that antibody. Such nomenclature would
potentially minimize confusion in the literature regarding the
sensitivity, specificity, phenotypic associations and clinical use of such
antibodies.
This brings us back to the study by Hengstman et al.1 Is it possible
that the differences in clinical associations noted in this paper, as
compared to those found in previous studies5, are due to the detection of
different antibody populations by different methods? Antibodies that bind
to fragments of the chromodomain helicase DNA binding protein 4 (the Mi-2
beta antigen) by ELISA may be quiet different than those which are
positive by immunodiffusion or which immunoprecipitate the Mi-2 antigen in
conjunction with the rest of the nucleosome remodeling and histone
deacetylase complex - the original ways that anti-Mi-2 autoantibodies and
their clinical associations were defined. It would have been useful for
the authors to have compared these methods directly in this study to
address this possibility. Until this possible methodologic difference is
resolved, however, perhaps it would be best to not define such ELISA-
binding antibodies as anti-Mi-2 autoantibodies, but rather as antibodies
which bind fragments of the chromodomain helicase DNA binding protein 4 by
ELISA.
References
(1) Hengstman GJ, Vree Egberts WT, Seelig HP et al. Clinical
characteristics of patients with myositis and autoantibodies to different
fragments of the Mi-2 beta antigen. Ann Rheum Dis 2006; 65(2):242-245.
(2) Fritzler MJ, Wiik A, Tan EM et al. A critical evaluation of
enzyme immunoassay kits for detection of antinuclear autoantibodies of
defined specificities. III. Comparative performance characteristics of
academic and manufacturers' laboratories. J Rheumatol 2003; 30(11):2374-
2381.
(3) Mathews MB, Bernstein RM. Myositis autoantibody inhibits
histidyl-tRNA synthetase: a model for autoimmunity. Nature 1983; 304:177-
179.
(4) Miller FW, Waite KA, Biswas T, Plotz PH. The role of an
autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of
autoimmunity. Proc Natl Acad Sci U S A 1990; 87(24):9933-9937.
(5) Love LA, Leff RL, Fraser DD et al. A new approach to the
classification of idiopathic inflammatory myopathy: myositis-specific
autoantibodies define useful homogeneous patient groups. Medicine
(Baltimore) 1991; 70(6):360-374.
I have read with interest the series of articles presenting the
development of a working atlas for Rheumatoid Arthritis scoring with MRI.
It will surely prove to be a useful and objective tool for the evaluation,
prognosis and follow-up of these patients. I find however, a practical
issue that could render this scoring system as somewhat cumbersome, unless
a better protocol for clinical MRI is develope...
I have read with interest the series of articles presenting the
development of a working atlas for Rheumatoid Arthritis scoring with MRI.
It will surely prove to be a useful and objective tool for the evaluation,
prognosis and follow-up of these patients. I find however, a practical
issue that could render this scoring system as somewhat cumbersome, unless
a better protocol for clinical MRI is developed.
In clinical practice, I have been increasingly receiving requisitions from
our rheumatologists for "bilateral hands and wrists, before and after
Gadolinium enhancement". Although I do have a hi-resolution 1.5 T system
with a dedicated wrist coil that can offer adequate spatial, contrast and
temporal resolution for the detection and scoring of bone erosion and
edema, Gadolinium enhancement for synovitis scoring is hindered by time
constraints already mentioned in the OMERACT- RAMRIS series of articles:
Since each wrist has to be imaged individually, after gadolinium is
administered, only one side could be adequately imaged in terms of time-after injection effects (temporal resolution).
In cases of unilateral symptoms, some would be inclined to image only the
clinically affected side; this could lead to non-detection of early
changes in the contralateral side.
In order to apply adequately the RAMRIS, two separate imaging sessions
would have to be scheduled, probably a couple of days apart. This is also
obviously impractical, especially for RA patients that are in pain.
Although I have no hard evidence, I do believe that STIR imaging with
current state-of-the art equipment, in which different weightings can be
achieved, should be capable of demonstrating clinically significant
degrees of edema and inflammation, not only of bones but of soft tissues,
and that STIR imaging in at least two planes, transverse and coronal, may
prove to be a better and more practical solution for this issue, allowing
complete imaging in a single appointment; even for patients that are not
in pain, this would be a significant improvement in medical care.
I would urge the OMERACT group experts to consider the development of a
similar scoring system and reference atlas based on images that can be
achieved in clinical practice without the mentioned limitations, such as
STIR images. Several questions remain to be answered: optimal planes of
imaging, FOVs, inversion times, TR/TE and all the other possible or
relevant technical parameter selection remain to be standardized at common
magnet strengths. Such a multicenter task group should be able to fulfill
the sample requirements and other methodological aspects needed for a well
-designed correlation between STIR images and gadolinium enhancement that
could answer this practical issue.
Sincerely Yours,
Anibal J. Morillo, MD
Institutional Radiologist
Department of Diagnostic Imaging
Fundación Santa Fe de Bogotá University Hospital
Calle 119 No. 9-33 P3
Bogotá, Colombia
Genetic factors not only plays an important role for development of
reactive arthritis in patients with Chlamydia infection, but genetic
factors also influence the susceptibility to such infections. Recently
recurrent Chlamydia infection have been found to be associated with human
leukocyte antigen variants (DRB1*03-DQB1*04 and DQB1*06). Again a G-C-C
haplotype corresponding to variants at IL-10 (e...
Genetic factors not only plays an important role for development of
reactive arthritis in patients with Chlamydia infection, but genetic
factors also influence the susceptibility to such infections. Recently
recurrent Chlamydia infection have been found to be associated with human
leukocyte antigen variants (DRB1*03-DQB1*04 and DQB1*06). Again a G-C-C
haplotype corresponding to variants at IL-10 (encoding interleukin-10 [IL-10]) promoter positions -1082, -819, and -592 has been found to be
underrepresented in individuals with recurrent infection. These genetic
associations are independent of nongenetic factors, including number of
sex partners, race, sex, duration of follow-up, and human immunodeficiency
virus type 1 seropositivity.
Consistent with the observed IL-10
association, cervical secretions in female adolescents without the IL-10 G-C-C haplotype have an elevated IL-10 concentrations after Chlamydia
infection, which may reflect involvement of a Chlamydia-specific mechanism
for genetically mediated, differential IL-10 expression in the genital
tract. This important observation will lead to better understanding of
aetiopathogenesis of Chlamydia infection and its sequelae such as reactive
arthritis, which requires further study.
Reference:
1. Wang C,Tang J,Geisler WM,Crowley-Nowick PA,Wilson CM and Kaslow RA.J
Infect Dis.2005 Apr 1;191(7):1084-92.
We read with interest the paper of M Sebastianni et al about the predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis(1). The authors suggest that the CSURI score "can represent a feasible and reliable clinical tool in the routine evaluation of patients". However, we feel this report raises serious issues concerning the reproducibility of the methodology. When calculating the score, the num...
Dear Editor,
Osteoarthritis can occur at almost any joint, osteoarthritis of the knee is the most common type. More than 10 million Americans have osteoarthritis of the knee. Most people affected are older than 45 years.[1]
The published article by K L Bennel et al. lacks patient’s information like patient’s age, sex, weights, heights, and family history. In this article K L Bennel et al. concluded that p...
Dear Editor,
We have read the reply from the authors to our letter. As a final remark we would like to repeat our previous statement: “From a clinician’s perspective we think that health economic analyses in RA should always be done with intimate knowledge of the patient cohort on which the calculations are based. Any projection and modelling in other settings must be carried out with great care in close collabora...
Dear Editor,
We read with interest the recent article “Smoking is a risk factor for anti-CCP antibodies only in RA patients that carry HLA-DRB1 Shared Epitope alleles” by Dr. Linn-Rasker and colleagues in Leiden.[1] The question of whether true gene-environment interaction exists between genotype (HLA-DRB1 shared epitope, SE) and an environmental exposure, cigarette smoking in this case, both of which are known to...
Dear Editor,
We read the study by Saraux et al (1) on the prevalence of Spondyloathropaties (SpA)s in France with great interest. In this well designed study, 9395 subjects were interviewed over the phone using a structured questionnaire. SpA was confirmed in 29 patients by the patient’s rheumatologist or by clinical examination. Of these 29 patients, 13 had ankylosing spondylitis (AS) and 11 had psoriatic arthri...
Dear Editor,
We found the study by Elkayam et al (1) of great interest, as it sheds more light on the complex scenario of anti cyclic citrullinated peptide antibodies (anti-CCP), originally described as highly specific for rheumatoid arthritis (RA). Indeed, it appears that an immune response to these proteins is initiated (though it’s not yet clear how sustained) in several other conditions. It is not surprising t...
Dear Editor,
We read with great interest the recently published article by Otero et al. [1] where they report significantly increased levels of leptin, adiponectin and visfatin plasma levels in patients with rheumatoid arthritis compared with controls. Their finding concerning the level of leptin in rheumatoid arthritis contradicts the results from other studies including our own (Ljung et al, submitted).[2][3] Our co...
Dear Editor,
I read with interest the recent study describing clinical characteristics associated with antibodies that bind fragments of the Mi-2 beta antigen1 and it raises the question of how to best define autoantibodies. For economic reasons, ELISAs are taking over much of the immunology testing in rheumatology practice today. ELISAs are being used despite their often limited validation and the many concerns...
Dear Editor,
I have read with interest the series of articles presenting the development of a working atlas for Rheumatoid Arthritis scoring with MRI. It will surely prove to be a useful and objective tool for the evaluation, prognosis and follow-up of these patients. I find however, a practical issue that could render this scoring system as somewhat cumbersome, unless a better protocol for clinical MRI is develope...
Dear Editor,
Genetic factors not only plays an important role for development of reactive arthritis in patients with Chlamydia infection, but genetic factors also influence the susceptibility to such infections. Recently recurrent Chlamydia infection have been found to be associated with human leukocyte antigen variants (DRB1*03-DQB1*04 and DQB1*06). Again a G-C-C haplotype corresponding to variants at IL-10 (e...
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