Increased serum IgA and decreased IgG3 strongly correlate with increased serum TGF-β1 levels in patients with nonimmune chronic idiopathic neutropenia of adults

Objective: To study the changes in serum immunoglobulins and some closely related pro-inflammatory cytokines in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). Methods. Serum levels of gamma-globulins, IgG, IgA, IgM, IgG subclasses, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and transforming growth factor-beta(1) (TGF-beta(1)) were evaluated in 83 NI-CINA patients and 65 normal controls using the respective conventional methods. Results: We found that serum gamma-globulin, IgG and IgG(1) levels were all significantly increased in the entire group of patients studied, compared to controls (p <0.001, p < 0.01 and p < 0.01, respectively), while the levels of IgG, were significantly reduced (p<0.001). Serum IgA were increased in patients with severe neutropenia (p< 0.001). No significant changes were noted in serum IgM, IgG(2) and IgG(4) levels. The infrequent occurrence of detectable amounts of IL-4 and IFN-gamma in the serum was similar in both, patients and control subjects. Serum levels of TGF-beta(1) were increased in all groups of patients studied and they correlated inversely with the levels of IgG, (p<0.001) and positively with the levels of IgA (p<0.001), suggesting the possible involvement of the cytokine in immunoglobulin class switching. Conclusion. Patients with NI-CINA have significant changes in serum immunoglobulins and some inflammation-related cytokines. These findings provide additional evidence for the existence of an unrecognized low-grade chronic inflammatory process in NI-CINA patients and coroborate our previously reported suggestion for the possible involvement of this inflammation in the pathogenesis of neutropenia in the affected subjects.