COMPARISON OF ALPHA-5(IV) COLLAGEN CHAIN EXPRESSION IN SKIN WITH DISEASE SEVERITY IN WOMEN WITH X-LINKED ALPORT-SYNDROME

X-Linked Alport syndrome is caused by mutations in the type IV collage n alpha 5 chain gene. Male patients usually develop end-stage renal di sease, whereas female patients have more variable phenotypes from asym ptomatic hematuria to end-stage renal disease. The variable phenotypes in female patients may be attributable to different X-chromosome inac tivation patterns. Therefore. the correlation between disease severity and the degree of alpha 5 chain expression in the epidermal basement membrane of female patients with X-linked Alport syndrome was examined . To estimate the disease severity in X-linked Alport syndrome, the ra tios of protein to creatinine in single voided urine samples were used . Expression of the alpha 5 chain in the epidermal basement membrane w as examined by an indirect immunofluorescence method using an anti-alp ha 5 chain monoclonal antibody. A total of 25 female patients with X-l inked Alport syndrome from 17 families was examined. Multiple regressi on analysis using disease severity as the response variable, and age, family history of nephritis, female and male family history of end-sta ge renal disease, serum creatinine concentration, and alpha 5(IV) expr ession ratio in the epidermal basement membrane as explanatory variabl es showed that only alpha 5(IV) expression ratio was a significant fac tor, and that it showed a highly significant negative association with disease severity (adjusted r(2) = 0.71, P = 0.0001). These findings s uggest that variable alpha 5 chain expression, possibly caused by diff erent X-inactivation patterns, is responsible for the variable disease severity in female patients with X-linked Alport syndrome, and that i mmunohistochemical examination of alpha 5 chain expression in the epid ermal basement membrane may be a simple and useful method for predicti ng patient outcome.