Background Anti-nuclear antibodies (ANAs) are autoantibodies binding to various components of the cell nucleus. ANAs are often detected in various systemic autoimmune diseases. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition of unknown etiology1) involving various organs. ANAs are detected in 15% of IgG4-RD patients1) and this fact is the basis of the suggestion that IgG4-RD may be autoimmune in nature. However, disease-specific ANAs such as anti-SS-A antibody and anti-dsDNA antibody remain to be clarified in IgG4-RD.
Objectives The present study was conducted to clarify the positive rate, titer, and clinical significance of ANAs in IgG4-RD.
Methods We enrolled 70 IgG4-RD patients (45 males, 25 females; mean age 64.1±1.2 years) diagnosed according to comprehensive diagnostic criteria for IgG4-RD2). The positive rate, titer and staining pattern of ANA in IgG4-RD patients using immunofluorescence method were retrospectively compared to those in 65 patients with systemic lupus erythematosus (SLE), 22 with anti-SS-A antibody positive Sjögren's syndrome (SjS), and 341 healthy controls (HC) who received medical examination. In addition, we analyzed the relationship between the titer of ANAs and serum IgG level in the IgG4-RD patients.
Results The ANA titers were as follows (Figure); 21 (30.0%) patients showed ≥1:40 and 7 (10.0%) patients ≥1:160 in IgG4-RD; 65 (100%) patients showed ≥1:40 and 55 (86.4%) ≥1:160 in SLE; 21 (95.5%) patients showed ≥1:40 and 19 (86.4%) ≥1:160 in SjS; 96 (30.9%) HC showed ≥1:40 and 5 (1.5%) ≥1:160. The dominant staining pattern of ANAs was homogenous (79.0%) in IgG4-RD, but speckled with/without homogenous in SLE (speckled 31.7%, speckled + homogenous 31.7%) and SjS (speckled 47.8%, speckled + homogenous 26.1%). Serum IgG level was not different between IgG4-RD patients showing ≤1:80 and ≥1:160 of ANAs (≤1:80, mean 2,084 mg/dL, range 1,078-5,358 mg/dL; ≥1:160, mean 3,068 mg/dL, range 1,765-4,661 mg/dL; p =0.078), although serum IgG levels tended to be high in cases in which ANAs revealed high titers.
Conclusions The positive rate, titer and staining pattern of ANAs in IgG4-RD were similar to those in HC, and are quite different from those in SLE and SjS. These results indicate that ANA detection is nonspecific in IgG4-RD, appearing according to serum IgG elevation. ANAs are not useful in the diagnosis and do not contribute to the pathogenesis in IgG4-RD.
Yamamoto M, Takahashi H, Shinomura Y. Mechanisms and assessment of IgG4-related disease: lessons for the rheumatologist. Nat Rev Rheumatol 2014; 10, 148-159.
Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012; 22, 21-30.
Disclosure of Interest None declared