P0347COMPLEMENT FACTOR BB AND FACTOR C4D IN IGA NEPHROPATHY AND IGA VASCULITIS
Authors: Westergren Emelie , Söderberg Magnus , Challis Benjamin , Wernerson Annika , Qureshi Abdul Rashid Tony , Bruchfeld Annette 
Published: June 2020

Abstract

Background and Aims
IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. IgAN and IgA Vasculitis with nephritis (IgAVN) are thought to have related pathogenesis characterized by IgA-containing renal immune complexes contributing to chronic kidney disease (CKD) and renal failure. In both diseases, IgA1 immune complexes and complement factors have been shown to be involved, indicating complement activation. However, the individual contribution of the alternative and lectin pathway has of yet not been fully elucidated. Plasma Bb is a marker of the alternative pathway activity and plasma C4d of the mannan-binding lectin pathway. We aimed to investigate the association between circulating plasma Bb and C4d at diagnosis and potential correlates with clinical features, renal histopathology and renal outcome in patients with IgAN and IgAVN.

Method
A prospective study of 98 patients undergoing renal biopsy was performed. Median age was 43 years, 52% males, 88% were caucasians, Sixty-six patients were diagnosed with IgAN, 15 IgAVN and 17 controls with “non-immunocomplex driven disease including Thin membrane disease, Diabetic Nephropathy, Minimal change disease or renal failure due to hyperfiltration. Blood samples were analyzed for complement factors C4d and Bb (both ELISA, Termo Fisher ScientificTM). Oxford classification of the renal biopsy was done at baseline and creatinine, estimated glomerular filtration rate (eGFR-CKD-EPI formula) were measured annually. Continuous data are expressed as median (25th to 75th percentile) and nominal or ordinal data as percentage. Comparisons between groups were assessed with the non-parametric Wilcoxon test/ Kruskal-Wallis ANOVA-test for continuous variables and Chi-square test for nominal variables.

Results
Patients with IgAN and IgAVN were significantly younger than the control group. There were no significant differences between the three groups for gender distribution and eGFR. Complement factor Bb for patients with IgAN and IgAVN was significantly increased (figure 1) as compared to the control group, whereas there was was no statistical difference for complement factorsC4d between groups. Estimated GFR decreased significantly only in patients with IgAN after 24 months of follow-up (56.6 ± 3.8 ml/min/1,73m2 as compared to IgAVN 83.8 ± 8.5 and controls 90.2 ± 8.9).
Patients with IgAN had more severe histopathological changes in T-score (T-score 0, 1, 2 in IgAN 51 %, 37 % and 12 % respectively) compared to IgAVN. In the IgAN group a more severe T-score was significantly associated with increased levels of complement factor Bb (p=0.005) but did not reach significance for complement factor C4d (p=0.097). No other difference or correlations were found with regards to M, E, S and C % scores.

Conclusion
Patients with IgAN were younger and had increased levels of complement factor Bb and after 24 months follow-up significantly reduced eGFR. The increase in factor Bb was also associated with more severe histopathological changes in T-score. These findings suggest that the alternative complement pathway contributes to the pathogenesis in IgAN and chronic kidney damage. Our findings should motivate studies in a larger population to further clarify the role of complement activity in IgAN and IgAVN.