Elsevier

Autoimmunity Reviews

Volume 9, Issue 10, August 2010, Pages 652-656
Autoimmunity Reviews

Review
Anti-NuMA1 and anti-NuMA2 (anti-HsEg5) antibodies: Clinical and immunological features: A propos of 40 new cases and review of the literature

https://doi.org/10.1016/j.autrev.2010.05.001Get rights and content

Abstract

Objective

Anti-NuMA1 and anti-NuMA2 antibodies are antinuclear antibodies (ANA) targeting the mitotic spindle apparatus. Our objective was to determine their clinical and immunological features and to review the literature available data.

Patients and methods

Between 2004 and 2008, 36,498 sera were analyzed for the presence of ANA, which included anti-NuMA1 and anti-NuMA2 antibodies. Clinical and immunological features of patients with positive anti-NuMA1 and anti-NuMA2 antibodies (titer  1/320) were retrospectively collected and analyzed. A review of the literature was secondly performed.

Results

Out of the 36,498 sera analyzed, 10,585 sera were positive for ANA (29%). Out of ANA positive sera, 40 sera (0.38%) (40 different patients) were positive for anti-NuMA antibodies: 27 anti-NuMA1 (0.26%) and 13 anti-NuMA2 (0.12%). Compared to anti-NuMA2 positive patients, anti-NuMA1 positive patients were more often female (81.5% versus 46%; P = 0.03), had more frequently a connective tissue disease (CTD) (40.7% versus 0%; P = 0.016) and higher serum titers (877 ± 466 versus 443 ± 278; P = 0.007). The anti-NuMA1 positive CTD were either Sjögren's syndrome (SS) (54.5%) or systemic lupus erythematosus (SLE) (45.5%). In the literature, 164 anti-NuMA positive patients (133 anti-NuMA1 and 31 anti-NuMA2) have been reported. Combining the reported cases to ours, up to 67.5% of anti-NuMA positive patients had an autoimmune disease, mostly pSS in 34% (31/90) and SLE in 31% (28/90). Anti-NuMA1 antibodies were the single positive ANA in 46% of anti-NuMA1 positive SS and 47% of anti-NuMA1 positive SLE, and anti-NuMA2 antibodies in 2/2 and 87.5%, respectively.

Conclusion

Detection of anti-NuMA1 and anti-NuMA2 antibodies is very uncommon. When present, they are mostly associated with connective tissue disease, mainly Sjögren syndrome and systemic lupus. Clinicians may be aware that in these latter conditions, anti-NuMA antibodies may be the single serological marker.

Introduction

Anti-Nuclear Mitotic Apparatus (NuMA) antibodies 1 and 2 belong to the family of auto-antibodies against mitotic spindle apparatus (MSA), a subtype of antinuclear antibodies (ANA), which have been described for the first time in 1981 [1]. Anti-NuMA1 and anti-NuMA2 differ by their antigenic target, anti-NuMA1 targeting the NuMA and anti-NuMA2 the Kinesin Eg5 (HsEg5) [2]. NuMA and HsEg5 are the most common spindle antigens. NuMA is a 236 kDa nuclear matrix protein, which is distributed to the pericentrosomal region at each spindle pole during mitosis. NuMA has been shown to be involved for the terminal phases of chromosome separation and/or nuclear reassembly. HsEg5 is a 115 kDa protein member of the BimC family of kinesin-like proteins, distributed throughout the spindle during cell division [2], [3], [4]. These features lead to a different immunofluorescent pattern between anti-NuMA1 and anti-NuMA2, anti-NUMA1 being detected in the interphase and mitotic cells and anti-NuMA2 antibodies only in mitotic cells [3] (Fig. 1).

Few studies have assessed the prevalence and clinical correlation of anti-NuMA1 and anti-NuMA2 antibodies. Their prevalence among sera tested for ANA is estimated to be less than 1% [5], [6]. They are reported to be associated with several conditions, mainly connective tissue diseases [4], [5], [6], [7], [8], [9], autoimmune liver disease [10] and infections [11].

In the present study, we assessed the prevalence and the clinical significance of anti-NuMA1 and 2 antibodies from a monocentre series of 40 patients, and secondly we reviewed the available data in the literature.

Section snippets

Patients

Between 2004 and 2008, 36,498 sera were tested for antinuclear antibody (ANA), including anti-NuMA1 and anti-NuMA2 antibodies in the department of clinical immunochemistry of a university hospital. We retrospectively collected and analyzed clinical and immunological data of patients with positive anti-NuMA1 and anti-NuMA2 antibodies. A review of the literature was secondary performed to compare our results to those previously reported.

Immunological tests

Antinuclear Antibodies (ANA) were detected using an indirect

Results

Out of the 36,498 sera analyzed between 2004 and 2008, 10,585 sera were positive for ANA (29%). Forty sera out of 10,585 ANA positive sera (0.38%), from 40 different patients, were positive for anti-NuMA1 and Anti-NuMA2 antibodies. Anti-NuMA1 antibodies were positive in 27 patients (0.26%) and anti-NuMA2 antibodies in 13 patients (0.12%). They included 28 women (70%) with a mean age of 53 ± 16.8 years. The mean titer of anti-NuMA antibodies was 736 ± 459. Clinical data were available for 38

Review of the literature

Since the first description of anti-NuMA antibodies, few studies have reported their clinical interest. To our knowledge, eight articles, which included 164 patients (133 patients with anti-NuMA1 and 31 patients with anti-NuMA2), are available (Table 2, Table 3). The prevalence of anti NuMA ranged from 0.23% to 0.9% [5], [6], [12]. A female gender predominance (141/155 = 91%) was usually observed. Main studies reported a close association of anti-NuMA1 and anti-NuMA2 with autoimmune diseases,

Discussion

In this study, we found the low prevalence (0.38%) of anti-NuMA antibodies among positive ANA (0.26% for anti-NuMA1 and 0.12% for anti-NuMA2). Our results showed a peculiar pathological profile of anti-NuMA1 antibodies, which were, compared to anti-NuMA2 antibodies, more frequently associated with a younger age, female gender, higher anti-NuMA serum titers and a definite autoimmune disease, i.e. pSS or SLE. In keeping with previous reports [4], [6], anti-NuMA positive autoimmune diseases were

Take-home messages

  • Anti-NuMA 1 and 2 antibodies are uncommonly detected and may represent 0.38% of antinuclear antibodies.

  • Anti-NuMA antibodies are associated with autoimmune diseases in up to two thirds of patients.

  • The most frequent anti-NuMA associated autoimmune diseases are systemic lupus erythematosous (SLE) and Sjögren syndrome (SS).

  • When positive, anti-NuMA antibodies are mostly isolated and not associated with other ANA, as in 74.5% of cases.

  • Anti-NuMA antibodies appear as possible serological markers of SS

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