ABSTRACT
We report the occurrence of congenital nephrotic-range proteinuria secondary to focal segmental glomerulosclerosis in an infant with epidermolysis bullosa and pyloric atresia. A homozygous missense mutation, R1281W, in exon 31 of the beta4 integrin gene, ITGB4, was identified. By immunofluorescence, beta4 integrin expression was reduced in both dermal keratinocytes and glomerular podocytes. This is the first demonstration of beta4 integrin expression in human glomeruli. We postulate a role for altered beta4 integrin function in the mediation of the glomerular permeability defect.
Subject(s)
Antigens, CD/genetics , Epidermolysis Bullosa, Junctional/complications , Glomerulosclerosis, Focal Segmental/congenital , Glomerulosclerosis, Focal Segmental/genetics , Integrins/genetics , Mutation, Missense , Dermis/chemistry , Exons/genetics , Fluorescent Antibody Technique , Glomerulosclerosis, Focal Segmental/complications , Glomerulosclerosis, Focal Segmental/pathology , Homozygote , Humans , Infant, Newborn , Integrin beta4 , Integrins/analysis , Kidney Glomerulus/chemistry , Kidney Glomerulus/pathology , Male , Pyloric Stenosis/complications , Pyloric Stenosis/congenitalABSTRACT
Autoimmune phenomena are common in human immunodeficiency virus (HIV) infection, yet systemic lupus erythematosus (SLE) and HIV infection rarely are seen concurrently in the same patient. Many of the cases of combined HIV infection and SLE reported in the literature are patients with SLE before HIV infection and who did not undergo renal biopsy at a time when both processes were present. We report the clinical manifestations and renal biopsy findings in four subjects with concurrent HIV infection and SLE and compare them with the seven previously reported cases in the literature. Taken together, most patients were black (91%) and male (73%), and approximately half (55%) were children with perinatal HIV infection. These demographics differ markedly from those of idiopathic SLE, a disease that predominantly affects female adults. Renal presentations included proteinuria and hypocomplementemia, frequently with hematuria and renal insufficiency. Renal biopsy findings in 10 cases included all classes of lupus nephritis (class IIb in two cases, class III in one case, class IV in three cases, class V in three cases, class III and V in one case), two of which also displayed overlapping features of HIV-associated nephropathy (HIVAN). One case had isolated findings of HIVAN. This cohort provides a unique population in which to study interacting pathomechanisms between HIV infection and SLE.