Autoantibodies in primary Sjögren's syndrome are directed against proteasomal subunits of the alpha and beta type

Arthritis Rheum. 1999 Apr;42(4):697-702. doi: 10.1002/1529-0131(199904)42:4<697::AID-ANR12>3.0.CO;2-H.


Objective: The proteasome subunit HC9 (alpha3) has recently been identified as a major target of the humoral autoimmune response in patients with autoimmune myositis and systemic lupus erythematosus. Since B cell hyperreactivity is a common feature of systemic autoimmune diseases, patients with primary Sjögren's syndrome (SS) and other control groups were investigated to evaluate the significance of autoantibodies against the proteasome.

Methods: Analyses of autoantibodies directed against the 20S proteasome were performed using enzyme-linked immunosorbent assay, immunoblot, and 2-dimensional electrophoresis. Forty-three patients with primary SS, 47 patients with rheumatoid arthritis including 9 with secondary SS, 19 patients with gastrointestinal tumors, and 80 healthy controls were tested for antiproteasome antibodies.

Results: Antiproteasome antibodies were detected in 39% of patients (17 of 43) with primary SS. In contrast, only 1 of 47 patients with rheumatoid arthritis showed positive reactivity (P < 0.001). Serum samples from 19 tumor patients (P < 0.003) and 80 healthy controls (P < 0.001) were serologically negative. Moreover, immunoblotting and 2-dimensional analysis of the antiproteasome response revealed a polyspecific recognition pattern in 7 patients with primary SS. Different proteasomal subunits of the alpha and beta type, including subunits that carried the proteolytic active sites, were recognized by the patients' sera.

Conclusion: The humoral antiproteasome response in primary SS, in contrast to its secondary form, is characterized by an extensive recognition pattern of several subunits, indicating a polyspecific B cell activation against the 20S proteasome. Moreover, proteolytically active beta-type subunits, which are important for the generation of major histocompatibility complex class I-restricted antigens, appear to be targets of the autoimmune response. The data indicate that the proteasome itself may stand on a cross point of pathways that links mechanisms of the immune defense with features of systemic autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antinuclear / immunology*
  • Antibody Specificity*
  • Cysteine Endopeptidases / analysis
  • Cysteine Endopeptidases / immunology*
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Multienzyme Complexes / analysis
  • Multienzyme Complexes / immunology*
  • Myositis / enzymology
  • Myositis / immunology
  • Proteasome Endopeptidase Complex
  • Sjogren's Syndrome / enzymology
  • Sjogren's Syndrome / immunology*


  • Antibodies, Antinuclear
  • Multienzyme Complexes
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex