Atypical Autoantibodies in Patients with Primary Sjögren Syndrome: Clinical Characteristics and Follow-Up of 82 Cases

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Objectives

To analyze the clinical characteristics, follow-up, and fulfillment of classification criteria for other systemic autoimmune diseases (SAD) in patients with primary Sjögren syndrome (SS) and atypical autoantibodies.

Methods

We studied 402 patients diagnosed with primary SS seen consecutively in our Department since 1994. We considered anti-DNA, anti-Sm, anti-RNP, antitopoisomerase1/Scl70, anticentromere (ACA), anti-Jo1, anti-neutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aPL), and lupus anticoagulant as atypical autoantibodies. The patients were prospectively followed after inclusion into the protocol, focusing on the development of features that might lead to the fulfillment of classification criteria for additional SAD. As a control group, we selected an age–sex-matched subset of patients with primary SS without atypical autoantibodies.

Results

Eighty-two (20%) patients showed atypical autoantibodies (36 had aPL, 21 anti-DNA, 13 ANCA, 10 anti-RNP, 8 ACA, 6 anti-Sm, 2 anti-Scl70, and 1 anti-Jo-1 antibodies). There were 77 (94%) women and 5 (6%) men, with a mean age of 57 years. Patients with atypical autoantibodies had no statistical differences in the prevalence of the main sicca features, extraglandular manifestations (except for a higher prevalence of Raynaud’s phenomenon, 28% versus 7%, P = 0.001), immunological markers, and in the fulfillment of the 2002 classification criteria, compared with the control group. After a follow-up of 534 patient-years, 13 (16%) of the 82 patients with atypical autoantibodies developed an additional SAD (systemic lupus erythematosus in 5 cases, antiphospholipid syndrome in 4, limited scleroderma in 3, and microscopic polyangiitis in 1) compared with none in the control group (P < 0.001).

Conclusions

This study shows an immunological overlap (defined by the presence of autoantibodies considered typical of other SAD) in 20% of our patients with primary SS. However, the clinical significance of these atypical autoantibodies varies widely depending on the autoantibodies detected, with a broad spectrum of prevalence and clinical patterns of disease expression, and a specific predilection for association with some SAD in preference to others.

Section snippets

Patients

We studied 402 patients diagnosed with primary SS seen consecutively in our Department since 1994. All patients fulfilled 4 or more of the preliminary diagnostic criteria for SS proposed by the European Community Study Group in 1993 (6) (including as mandatory criterion either positive immunological markers or salivary lip biopsy) and underwent a complete history and physical examination. Diagnostic tests for SS (rose bengal staining, Schirmer test, parotid scintigraphy, and salivary gland

General Description

Eighty-two (20%) patients had atypical autoantibodies (Table 1): 36 had antiphospholipid antibodies (aPL) (19 positive IgG-aCL, 19 LA, and 6 IgM-aCL), 21 positive anti-DNA antibodies, 13 ANCA, 10 anti-RNP, 8 ACA, 6 anti-Sm, 2 anti-Scl70, and 1 anti-Jo-1 antibodies. In 15 patients, more than 1 of these autoantibodies were detected. There were 77 (94%) women and 5 (6%) men (female:male ratio, 15:1), with a mean age at protocol inclusion of 57.3 ± 1.77 years (range, 20 to 87). A retrospective

Discussion

The diagnosis of SAD is a clinical challenge based on the application of internationally agreed sets of classification criteria that often combine diverse organ-specific manifestations with findings of circulating autoantibodies. In primary SS, the clinical significance of autoantibodies considered typical of other SAD is controversial. We have identified 224 previously reported cases with atypical autoantibodies (Table 2) (8, 10, 11, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,

References (61)

  • C. Vitali et al.

    Preliminary criteria for the classification of Sjogren’s syndrome

    Arthritis Rheum

    (1993)
  • C. Vitali et al.

    Classification criteria for Sjogren’s syndromea revised version of the European criteria proposed by the American-European Consensus Group

    Ann Rheum Dis

    (2002)
  • A.L. Fauchais et al.

    Antiphospholipid antibodies in primary Sjogren’s syndromeprevalence and clinical significance in a series of 74 patients

    Lupus

    (2004)
  • R. Cervera et al.

    Antiphospholipid antibodies in primary Sjogren’s syndromeprevalence and clinical significance in a series of 80 patients

    Clin Exp Rheumatol

    (1997)
  • P. Zufferey et al.

    Primary Sjögren syndrome preceding systemic lupus erythematosusa retrospective study of 4 cases in a cohort of 55 SS patients

    Lupus

    (1995)
  • M. Satoh et al.

    Development of anti-Sm and anti-DNA antibodies followed by clinical manifestation of systemic lupus erythematosus in an elderly woman with long-standing Sjogren’s syndrome

    Lupus

    (1995)
  • J. Font et al.

    Antineutrophil cytoplasmic antibodies in primary Sjögren’s syndromeprevalence and clinical significance

    Br J Rheumatol

    (1998)
  • A.E. Ghavari et al.

    Anticardiolipin antibodiesisotype distribution and phospholipid specificity

    Ann Rheum Dis

    (1987)
  • J.T. Brandt et al.

    Laboratory identification of lupus anticoagulantsresults of The Second International Workshop for identification of lupus anticoagulants

    Thromb Haemost

    (1995)
  • M.C. Hochberg

    Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus

    Arthritis Rheum

    (1997)
  • Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association diagnostic and therapeutic criteria committee

    Arthritis Rheum

    (1980)
  • A. Bohan et al.

    Polymyositis and dermatomyositis

    N Engl J Med

    (1975)
  • D. Alarcon-Segovia et al.

    Classification and diagnostic criteria for mixed connective tissue disease

  • W.A. Wilson et al.

    International consensus statement on preliminary classification criteria for definite antiphospholipid syndromereport of an international workshop

    Arthritis Rheum

    (1999)
  • J.C. Jennette et al.

    Nomenclature of systemic vasculitides. Proposal of an international consensus conference

    Arthritis Rheum

    (1994)
  • S.B. Ingram et al.

    An unusual syndrome of a devastating noninflammatory vasculopathy associated with anticardiolipin antibodiesreport of two cases

    Arthritis Rheum

    (1987)
  • R.A. Arroyo et al.

    Anticardiolipin antibodies in patients with primary Sjögren’s syndrome

    Arthritis Rheum

    (1989)
  • Y.L. Pennec et al.

    Serial measurements of anticardiolipin antibodies in primary Sjögren’s syndrome

    Clin Exp Rheumatol

    (1991)
  • R.A. Asherson et al.

    Antiphospholipid antibodies and HLA associations in primary Sjogren’s syndrome

    Ann Rheum Dis

    (1992)
  • A. Jedryka-Goral et al.

    Isotype profile and clinical relevance of anticardiolipin antibodies in Sjogren’s syndrome

    Ann Rheum Dis

    (1992)
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