Expression of mesangial IgA nephropathy in a family with several HLA‐dentical members

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SUMMARY: The familial incidence of mesangial IgA nephropathy (IgAN) is well recognized. However, the genetic implications of this finding remain uncertain. We report a family of East Timorese origin where six out of eight members, including the mother and five first‐degree offspring, have had histologically proven mesangial IgAN. All eight members have undergone HLA A, B, C and DR typing as well as determination of C4 allotype. Among the offspring, there are HLA‐identical male twins (A11,‐; B13,15; Cw3,‐; DR2,3) and three HLA‐identical females (A11,‐; B13,27; Cw3,‐; DR2,3). Their C4 allotype is also identical (i.e. A3; B1,2,96 and A3; B1,96, respectively). There were histological and biochemical differences between the twins: subject ii‐2 showed focal mesangial proliferation on light microscopy and a 24 h urine protein excretion of 1–2 g on presentation while subject ii‐3 was normal at that time. the latter subsequently underwent a renal biopsy 15 years later and this showed changes only on immunofluorescence microscopy. There were major differences in expression of renal disease among the HLA‐identical sisters: two developed end‐stage renal failure (ESRF) by the age of 30 years, while the third retains normal renal function after 15 years follow‐up. the angiotensin converting enzyme (ACE) genotype was examined for insertion (I)/deletion (D) polymorphism; this showed that both patients with severe renal disease had the ID genotype and this was also present in the two unaffected female members. the study shows no relationship between the HLA A, B, C, DR, C4 supratype and progress of renal disease in this family with mesangial IgAN. Moreover, no association could be demonstrated between progress and the ACE genotype, although the number of patients involved was small. the data suggest that environmental factors and/or genetic/environmental interaction influence the severity of renal injury.