ESPN 53rd Annual Meeting

ESPN 2021


 
Rituximab for the treatment of Anti-factor H autoantibody-associated C3 glomerulopathy: is it effective?
FEDERICA ZOTTA 1 ALESSANDRA GIANVITI 1 LAURA LUCCHETTI 1 ELISABETTA VALOTI 2 ELENA BRESIN 2 ANTONIO GARGIULO 1 MANUELA COLUCCI 1 FRANCESCO EMMA 1 MARINA VIVARELLI 1

1- IRCCS, DIVISION OF NEPHROLOGY AND DIALYSIS BAMBIN GESU PEDIATRIC HOSPITAL, ROME ITALY
2- IRCCS, INSTITUTE OF PHARMACOLOGICAL RESEARCH , MARIO NEGRI, BERGAMO, ITALY
 
Introduction:

 Autoantibodies targeting factor H (AB-FH), which is a crucial alternative pathway (AP) of complement regulatory protein, have been described in 1-3% of C3 glomerulopathy patients. It may be hypothesized that in their presence, which leads to uncontrolled AP activation, B cell depletion with rituximab may be effective

Material and methods:

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Results:

 CASE REPORT: A 10-yr old girl was admitted to our department for an occasional finding of proteinuria (protein/creatinine ratio 2.32 mg/mg), microscopic hematuria (60-150 blood cells per field) and anemia (9,2 g/dl). She had no history of serious illness or any recent evidence of upper respiratory or gastrointestinal tract infection.  Her physical examination was normal. Laboratory findings revealed normal renal function, absence of nephrotic syndrome. Low levels of C3 (3 mg/dl)  and C4 (6 mg/dl) were observed with elevated sC5b9 (2270 ng/ml), ANA and anti-dsDNA were normal.  The first kidney biopsy revealed a membranoproliferative glomerulonephritis with a full house immunofluorescence pattern. A low-salt diet, oral prednisone and mycophenolate were immediately started. A second biopsy, performed 3 months later showed a more proliferative pattern with mainly granular deposit of C3 detected by immunofluorescence. Treatment with 3 methylprednisolone pulses were added. Screening for complement abnormalities showed no genetic mutations in the genes coding for FH, FI, MCP, THBD, C3, C5, CFHR1-5, FB and DGKE. However, AB-FH (1069 AU/ml, upper limit of normal >127 AU/ml) was found to be positive and Rituximab infusion (375 mg/m2) was administered. Interestingly, AB-FH titer was not significantly reduced by Rituximab (739 AU/ml at 4 months) without any effect on proteinuria in the following months

Conclusions:

 To the best of our knowledge, this is the first report on the use of Rituximab in a patient with AB-FH-associated C3 glomerulopathy.

Large collaborative studies are needed to elucidate the best therapeutic strategy for this ultra-rare disease.