RESUMO
Anti-human upstream-binding factor (anti-hUBF) antibodies have been reported predominantly in patients with connective tissue diseases (CTDs); these have also been reported in patients without CTDs such as hepatocellular carcinoma. Because of the low frequency of expression and few case reports, there is no consensus on the clinical significance of these antibodies. Thus, we aimed to examine the clinical features of patients with anti-hUBF antibodies and analyzed 1042 patients with clinically suspected CTDs. The presence of anti-hUBF antibodies was screened using immunoprecipitation assays. Of the 1042 patients, 19 (1.82%) tested positive for anti-hUBF antibodies; among them, 10 (56%) were diagnosed with undifferentiated CTD (UCTD), six with systemic sclerosis (SSc) and three with other diseases. Five of the 10 patients with UCTD were referred to our hospital with suspected SSc. None of the five patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria, but three scored seven points, a relatively high score. Six anti-hUBF-positive patients with SSc had a significantly lower modified Rodnan skin score (mRSS) than that of anti-hUBF-negative patients with SSc (2 [0-2] vs 7 [0-49], p < 0.01). Compared with anti-topoisomerase I-positive patients, anti-hUBF-positive patients had a significantly lower mRSS (2 [0-2] vs 13 [0-42], p < 0.01) and lower incidence of scleroderma renal crisis (0 of 6 vs 8 of 184, p < 0.01). Compared with anti-centromere-positive patients, anti-hUBF-positive patients had a higher incidence of interstitial lung disease (ILD), but the difference was not statistically significant (4 of 6 vs 19 of 239). In conclusion, anti-hUBF antibodies were predominantly detected in patients with CTDs and UCTD. In patients with CTDs, SSc exhibited a high ratio, displaying a lower mRSS and higher incidence of ILD. In patients with UCTD, careful follow-up is recommended as they may develop CTDs in the future.
RESUMO
OBJECTIVES: In systemic sclerosis (SSc), B cell hyperactivation and abnormality are considered to play an important role in the disease pathophysiology. We aimed to clarify if the abnormal activation of B cells involves inhibitory FcγRIIB on B cells in SSc patients. METHODS: Blood samples were collected from 76 SSc patients (38 limited cutaneous SSc and 38 diffuse cutaneous SSc) and 59 healthy controls. We evaluated the expression levels of FcγRIIB on different B cell subsets. B cells were classified into five subsets based on their surface phenotype as measured by flow cytometry: naïve B cells (CD19+IgD+CD27-), pre-switched memory B cells (CD19+IgD+CD27+), double-negative (DN) memory B cells (CD19+IgD-CD27-), switched memory B cells (CD19+IgD-CD27mid), and plasmablasts (CD19+IgD-CD27high). The expression levels of the activation markers CD80, CD86, and CD95 were also examined. RESULTS: The expression levels of FcγRIIB on SSc naïve and DN memory B cells were significantly increased compared to healthy controls (p<0.05 and p<0.001, respectively). CD80, CD86, and CD95 expression levels were significantly higher in all five B cell subsets, except for CD80 in switched memory B cells and plasmablasts. Increased FcγRIIB expression levels on DN memory B cells were associated with disease activity as assessed by the European Scleroderma Study Group Activity Index, presence of interstitial lung disease (ILD), and reduced lung function. Intravenous cyclophosphamide pulse therapy decreased FcγRIIB expression levels on memory B cell subsets. CONCLUSIONS: SSc B cells may exhibit compensatory elevation in the expression levels of FcγRIIB in order to suppress the abnormal activation of B cells. In addition, FcγRIIB expression levels may serve as a marker of severe complications, such as ILD, in SSc.
