Anti-glomerular basement membrane nephritis and bullous pemphigoid caused by distinct anti-alpha 3(IV)NC1 and anti-BP180 antibodies in a patient with Crohn's disease.
BACKGROUND
Anti-glomerular basement membrane (GBM) nephritis is a rare disease induced by antibodies directed against alpha3(IV)NC1, the Goodpasture antigen. We report a patient with Crohn's disease who developed anti-GBM nephritis and the skin blistering disorder bullous pemphigoid, owing to distinct autoantibodies.


METHODS
Frozen sections of skin and kidney biopsies were incubated with antisera specific for human IgG, IgA, IgM, fibrin, and C3. Reactivity of the patient's serum with GBM antigens was studied by Western blot using bovine solubilized type IV collagen and by enzyme-linked immunosorbent assays using alpha1(IV), alpha3(IV), and alpha5(IV)NC1 recombinant proteins. Reactivity studies against skin antigens were done by Western blot using human keratinocyte and dermal extracts and three recombinant forms of the bullous pemphigoid antigen180 (BP180, also called BPAG2 or type XVII collagen). The patient's serum was affinity fractionated on a (IV)NC1 column, and the bound and unbound fractions were analyzed for their reactivity against GBM and skin antigens.


RESULTS
The patient had deposits of IgG along the GBM and the epidermal basement membrane zone. Circulating IgG antibodies against alpha3(IV)NC1 were detected. The patient's autoantibodies immunoblotted the intracellular domain but not the extracellular domain of BP180. Reactivity of the patient's IgG with BP180 was found only in the unbound fraction of the serum.


CONCLUSIONS
The simultaneous development of a rare renal and skin autoimmune disorder, resulting from non-cross-reactive autoantibodies, suggests that a common triggering event could be responsible for the autoimmune injury.
Plaisier
Emmanuelle
E
INSERM U489 and Department of Nephrology, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. emmanuelle.plaisier@tnn.ap-hop-paris.fr
Borradori
Luca
L
Hellmark
Thomas
T
Wattiaux
Marie-José
MJ
Flageul
Béatrice
B
Mougenot
Béatrice
B
Ronco
Pierre
P
D000328:Adult; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D001324:Autoantigens / Q000276:immunology*; D024141:Collagen Type IV / Q000276:immunology*; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000188:drug therapy / Q000276:immunology*; D000097805:Collagen Type XVII
D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D003520:Cyclophosphamide; D007166:Immunosuppressive Agents; D008775:Methylprednisolone; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C057112:type IV collagen alpha3 chain