Dysregulation of complement factor H in juvenile-onset systemic lupus erythematosus patients

Objectives: This study aims to evaluate the expression pattern of factor H in peripheral blood and the frequency of factor H autoantibodies in plasma of juvenile-onset systemic lupus erythematosus (jSLE) patients compared to healthy controls. Patients and methods: Between March 2019 and October 2019, a total of 30 healthy individuals (3 males, 27 females; mean age: 26±7.4 years; range, 18 to 40 years) and 65 jSLE patients (age of onset ≤16 years) (2 males, 63 females; mean age: 23.4±7 years; range, 15 to 38 years) were included. Factor H expression pattern was examined in blood of all subjects using quantitative real-time polymerase chain reaction and the frequency of factor H autoantibodies was estimated in plasma using enzyme-linked immunosorbent assay. Results: Factor H expression was significantly downregulated in jSLE patients compared to healthy controls (p<0.01). A significant underexpression of factor H was observed in jSLE patients with nephritis compared to those without nephritis (p<0.03), while there was no association of factor H expression levels with any of the other clinical and serological features, disease activity or disease damage index of patients. Only 5% of jSLE patients were positive for factor H autoantibodies without any correlations with the clinical data or disease activity of patients. Conclusion: Our study results suggest that factor H expression can be dysregulated in jSLE patients.

IgM Autoantibodies to Complement Factor H in Atypical Hemolytic Uremic Syndrome

BackgroundAtypical hemolytic uremic syndrome (aHUS), a severe thrombotic microangiopathy, is often related to complement dysregulation, but the pathomechanisms remain unknown in at least 30% of patients. Researchers have described autoantibodies to complement factor H of the IgG class in 10% of patients with aHUS but have not reported anti-factor H autoantibodies of the IgM class.MethodsIn 186 patients with thrombotic microangiopathy clinically presented as aHUS, we searched for anti-factor H autoantibodies of the IgM class and those of the IgG and IgA classes. We used immunochromatography to purify anti-factor H IgM autoantibodies and immunoenzymatic methods and a competition assay with mapping mAbs to characterize interaction with the target protein.ResultsWe detected anti-factor H autoantibodies of the IgM class in seven of 186 (3.8%) patients with thrombotic microangiopathy presented as aHUS. No association was observed between anti-factor H IgM and homozygous deletions involving CFHR3-CFHR1. A significantly higher proportion of patients with bone marrow transplant–related thrombotic microangiopathy had anti-factor H IgM autoantibodies versus other patients with aHUS: three of 20 (15%) versus four of 166 (2.4%), respectively. The identified IgM autoantibodies recognize the SCR domain 19 of factor H molecule in all patients and interact with the factor H molecule, inhibiting its binding to C3b.ConclusionsDetectable autoantibodies to factor H of the IgM class may be present in patients with aHUS, and their frequency is six-fold higher in thrombotic microangiopathy forms associated with bone marrow transplant. The autoantibody interaction with factor H’s active site may support an autoimmune mechanism in some cases previously considered to be of unknown origin.