Serum immunoglobulins and the risk of rheumatoid arthritis

doi:10.1136/ard.56.6.351

Annals of the Rheumatic Diseases 1997;56:351-356; doi:10.1136/ard.56.6.351

Ann Rheum Dis 1997;56:351-356 ( June )

Extended reports

Serum immunoglobulins and the risk of rheumatoid arthritis K Aho,^a M Heliövaara,^a P Knekt,^a A Reunanen,^a A Aromaa,^a A Leino,^b P Kurki,^c R Heikkilä,^c T Palosuo^a

^a National Public Health Institute, Helsinki , ^b Social Insurance Institution, Research and Development Centre, Turku , ^c United Laboratories Ltd, Helsinki

Correspondence to: Dr K Aho, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.

Accepted for publication 3 April 1997

OBJECTIVE $---$ Rheumatoid arthritis (RA) is associated with several autoantibodies that can precede the clinical disease. The immunoglobulinconcentrations in serum samples before illness were studied tolearn more about the immunological process beforeRA.
METHODS $---$ A case-control study was nested within a Finnish cohort of 19 072 adults who had neither arthritis nor a history of it atthe baseline examination during 1973-1977. By late 1989, 124 haddeveloped RA, of which 89 were positive for rheumatoid factor(RF). Three controls per each incident case were individuallymatched for sex, age, and municipality. The concentrations ofIgG, IgA, and IgM were measured from stored serumsamples.
RESULTS $---$ Serum IgG before illness was found to be directly proportional to the risk of RF positive RA, and a non-linear associationwas present between serum IgA and the risk of RF positive RA.These associations were constant between men and women and othersubgroups of the study population and not confounded by serumorosomucoid concentration, level of education, smoking, alcoholintake or body mass index. As adjusted for these factors, theodds ratios (95% confidence intervals) of RF positive RA in thelowest, mid, and highest tertiles of IgG distribution were 1.00,1.55 (0.81, 2.97), and 2.22 (1.16, 4.26), and in the tertilesof IgA 1.00, 2.23 (1.14, 4.36), and 1.78 (0.89, 3.57), respectively.The associations persisted throughout the entire observation periodbut were most distinct when the period to the onset of clinicalRA was $>=$ 10 years. IgM carried no predictive significance. Noneof the serum immunoglobulins predicted the development of RF negativeRA.
CONCLUSIONS $---$ Increased IgG levels may reflect some, at present unknown process in the early events leading to the development of RA, typicallyoccurring $>=$ 10 years before the onset of clinicaldisease.

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