Strong and selective glomerular localization of CD134 ligand and TNF receptor-1 in proliferative lupus nephritis.
CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family that can be expressed on activated T lymphocytes. Interaction between CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte activation, and in T cell adhesion to endothelium. To examine the possible role of this interaction in the pathogenesis of systemic lupus erythematosus (SLE), expression of CD134 and CD134L on peripheral blood leukocytes was studied, and no significant differences between SLE patients and control individuals were found. Immunohistology on renal biopsies from patients with lupus nephritis or other renal disorders, using a recombinant human CD134-containing chimeric molecule to detect CD134L, demonstrated the abundant presence of CD134L in all cases of proliferative lupus nephritis in a granular distribution predominantly along the epithelial side of the glomerular capillary wall. Confocal laser scanning microscopy indicated colocalization with subepithelial immune deposits. In none of the other renal disorders examined, including nonproliferative forms of lupus nephritis, was glomerular staining for CD134L detected in a similar pattern. Endothelial CD134L expression was frequently observed in different types of vasculitis. CD134 was detected on perivascular infiltrating leukocytes and on part of the tubular epithelium, but not on glomerular resident cells. Immunohistology for several other TNF(R) family members revealed in proliferative lupus nephritis a similar distribution for TNFR1 as was observed for CD134L. In contrast, glomerular expression of TNFR2 was similar in all cases examined. The glomerular presence of CD134L and TNFR1 in proliferative lupus nephritis in association with subepithelial immune deposits may be of pathogenetic significance and have diagnostic value.
Aten
Jan
J
Department of Pathology, (Renal Transplant Unit), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Roos
Anja
A
Department of Pathology, (Renal Transplant Unit), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Claessen
Nike
N
Department of Pathology, (Renal Transplant Unit), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Schilder-Tol
Esther J M
EJM
Department of Pathology, (Renal Transplant Unit), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ten Berge
Ineke J M
IJM
Department of Internal Medicine (Renal Transplant Unit), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Weening
Jan J
JJ
Department of Pathology, (Renal Transplant Unit), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D002455:Cell Division; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000378:metabolism; D008181:Lupus Nephritis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012016:Reference Values; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D008024:Ligands; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha