Clinical significance of criterial and non-criterial autoantibodies in systemic lupus erythematosus

Abstract

Objective: to determine the frequency of systemic lupus erythematosus (SLE)-specific (criterial) and non-specific (non-criterial) antibodies and their association with type I interferon (IFN) overexpression and clinical and laboratory manifestations of the disease. Material and methods . This single-center cross-sectional study included 140 patients (88% women) with a definite diagnosis of SLE who met the 2012 SLICC criteria. Median age at inclusion was 34 [26; 41] years, disease duration was 3.4 [0.4; 12.0] years, SLEDAI-2K score was 6.5 [4.0; 10.5] points, and SDI damage index was 0 [0; 2] points. Three IFN-stimulated genes (MX1, RSAD2, and EPSTI1) were selected to assess the IFN signature. Results and discussion . The most common autoantibodies were antibodies to double-stranded DNA (anti-dsDNA, 69%), C1q (anti-C1q, 43%), Ro/SSA (anti-Ro/SSA, 22%), and phospholipids (aPL, 17%), whereas the least common were antibodies to La/SSB (anti-La/SSB, 1%), RNP70 (anti-RNP70, 10%), Sm (anti-Sm, 11%), and rheumatoid factor (RF, 11%). The IFN signature was present in 55 (72%) of 76 patients. Discoid lupus erythematosus was associated with anti-Sm, subacute cutaneous lupus erythematosus with anti-Ro/SSA, and acute cutaneous lupus erythematosus (ACLE) with IFN-I; overall skin involvement, as well as ACLE, was less common in the presence of RF. Non-scarring alopecia, mucosal involvement, and Raynaud’s phenomenon were associated only with anti-Sm positivity; serositis with anti-C1q and anti-La/SSB; joint involvement and hemolytic anemia with anti-dsDNA, anti-C1q, and anti-Sm; leukopenia/lymphopenia with anti-dsDNA and IFN-I; thrombocytopenia with anti-Sm and aPL; and cryoglobulinemia with anti-C1q and anti-Ro/SSA. An interesting finding was the association of nephritis only with anti-dsDNA and anti-C1q, but not with hypocomplementemia. Anti-dsDNA, anti-C1q, and anti-Sm, which are not included in any SLE activity indices, were associated with the SLEDAI-2K activity index. Anti-dsDNA positivity was associated with an earlier age at SLE diagnosis, including childhood onset, whereas anti-Ro/SSA positivity, in contrast, was associated with later onset of the first disease symptom. Conclusion. Disease activity and most clinical manifestations characteristic of SLE are associated primarily with specific autoantibodies, including anti-dsDNA and anti-Sm, whereas among non-criteria autoantibodies, only anti-C1q showed such associations. The IFN signature was associated with the frequency and level of anti-dsDNA in the absence of hypocomplementemia, but not with anti-C1q or antibodies to RNA-associated proteins. Serological monitoring, including determination of anti-C1q, the most common non-criterial autoantibody, and anti-Sm, is recommended for assessing the risk of SLE relapse.