TABLE 1.

Histologic diagnosis, complement assessment and genetic screening of patients recruited selected from the Italian Registry of MPGN and classified into clusters using the three-step algorithm.

	Cluster 1 (n = 66)	Cluster 2 (n = 49)	Cluster 3 (n = 33)	Cluster 4 (n = 51)	Overall P-value
IC-MPGN (n = 96)	21.2%	89.8%	12.1%	66.7%	<0.0001
C3GN (n = 74)	78.8%	10.2%	0%	33.3%	<0.0001
DDD (n = 29)	0%	0%	87.9%	0%	<0.0001
Sex,% men	57.6%	49%	63.6%	60.8%	0.54
Age (yr)-Mean (SD)	14 (±10.7)	18.6 (±13.7)	15.3 (±10.2)	26.9 (±19.5)a,b,c	<0.001
Serum C3 (mg/dl)	29.1 (±19.8)	22.8 (±21.9)	35.4 (±34.3)	93.2 (±26.1)a,b,c	<0.001
Serum C4 (mg/dl)	18.7 (±6.7)	16.8 (±11.3)	20.6 (±8.7)	21 (±10)	0.11
Plasma sC5b-9 (ng/ml)	1378 (±1255)c,d	1861 (±1357)c,d	540 (±604)a,b	302 (±145)a,b	<0.001
Low serum C3	100%	100%	93.9%	49%a,b,c	<0.001
Low serum C4	7.7%	28.6%a,c,d	6.2%	10%	0.004
Low serum C3 and normal C4	92.3%b	71.4%a	87.5%	44%a,c	<0.001
High plasma sC5b-9	76.3%	83%	32.3%a,b	20%a,b	<0.001
RV carriers	27.3%	22.4%	15.2%	3.9%a,b	0.01
C3NeF positive	53.4%	62%	79.3%a	5.9%a,b,c	<0.001
RV carriers and/or C3NeF	71.6%	74.5%	82.8%	9.8%a,b,c	<0.001
FH levels (mg/L)	301.9 (±70.9)	284.5 (±72)	275.7 (±65)	322.5 (±76)b,c	0.02
Low FH levels	6.9%	8.7%	6.9%	0%	0.26
Anti-FH antibodies	1.7%	6.5%	10.3%	0%	0.08

Quantitative variables are expressed as mean (±SD). Abbreviations and limit of normal range: C3: 90–180 mg/dl. C4: 10–40 mg/dl; Normal plasma sC5b-9 levels: ≤400 ng/ml; Normal serum/plasma FH levels: ≥193 mg/L; RV, rare variant defined as genetic variant in coding and splicing regions of complement genes already related to C3G- IC-MPGN (CFH, CFI, CD46, CFB, C3, and THBD) with minor allele frequency (MAF) in the gnomAD database <0.001 and with Combined Annotation Dependent Depletion (CADD) phred score ≥10; p-values were corrected for multiple tests. ^aSignificant different from cluster 1; ^bsignificant different from cluster 2; ^csignificant different from cluster 3; ^dsignificant different from cluster 4.