ESPN 51th Annual Meeting

ESPN 2018


 
C4d immunofluorescence in pediatric forms of glomerulonephritis
RAFFAELLA LABBADIA 1 FRANCESCA DIOMEDI CAMASSEI 2 FEDERICA RITA SALUTARI 2 LAURA LUCCHETTI 1 MARINA VIVARELLI 1 FRANCESCO EMMA 1

1- DIVISION OF NEPHROLOGY AND DIALYSIS, BAMBINO GESù CHILDREN’S HOSPITAL, IRCCS, ROME, ITALY
2- DEPARTMENT OF LABORATORIES, PATHOLOGY UNIT, BAMBINO GESù CHILDREN’S HOSPITAL, IRCCS, ROME, ITALY
 
Introduction:

The term C3 Glomerulopathy (C3G) defines glomerular diseases characterized by dysregulated activation of the complement alternative pathway. Diagnosis is based on renal biopsy, and immunofluorescence typically shows a C3-dominant picture. However, old and new evidence shows that the immunofluorescence picture can be characterized by a wide variability. Therefore, differential diagnosis between complement-mediated and immune-mediated forms can be challenging. In an adult cohort of patients, negativity of glomerular C4D immunofluorescence, , an expression of the deposition of immune complexes that trigger the classic pathway of complement, was shown to be useful in identifying C3G (Sethi S, JASN 2015). The aim of our study was to evaluate whether glomerular C4d staining of renal biopsies could be helpful for the differential diagnosis between C3G and other types of glomerulopathies also in children.

Material and methods:

Our study included 67 renal biopsies suggestive of acute post-streptococcal GN (14), Full House Nephropathy (12), Lupus Nephritis (11) and C3 Glomerulopathy (30), performed between 2005 and 2017 in 67 children (39 males, 28 females) aged 9.1 ± 3.8 years.

Results:

Evaluation of immunofluorescence showed that C4d was “positive” (intensity 1+ to 3+) in 57 % of C3G cases, with no statistical difference compared to APSGN (57% positive, p=0,928 vs C3G) and, on the contrary, significant difference with FHNs (92%, p=0,030, vs C3G) and with LNs (91%, p=0,040 vs C3G), both classical immune-mediated glomerulonephritis.

Conclusions:

In children, C4d immunofluorescence positivity cannot be used as an exclusion marker for the diagnosis of C3G, as it is present in the majority of patients. C4d glomerular staining may, at least in part, be linked to an activation of the lectin pathway by an infectious process. Therefore, the discrepancy with previous adult studies may depend on the fact that children are more susceptible to infectious processes triggering the lectin pathway of complement with C4d deposition.