BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus.

Stohl, William; Xu, Dong; Kim, Kyoung Soo; Koss, Michael N; Jorgensen, Trine N; Deocharan, Bisram; Metzger, Troy E; Bixler, Sarah A; Hong, Yeon Sik; Ambrose, Christine M; Mackay, Fabienne; Morel, Laurence; Putterman, Chaim; Kotzin, Brian L; Kalled, Susan L

Stohl, William; Xu, Dong; Kim, Kyoung Soo; Koss, Michael N; Jorgensen, Trine N; Deocharan, Bisram; Metzger, Troy E; Bixler, Sarah A; Hong, Yeon Sik; Ambrose, Christine M; Mackay, Fabienne; Morel, Laurence; Putterman, Chaim; Kotzin, Brian L; Kalled, Susan L.

Afiliación

Stohl W; Division of Rheumatology, University of Southern California Keck School of Medicine, Los Angeles 90033, USA. stohl@usc.edu

Arthritis Rheum ; 52(7): 2080-91, 2005 Jul.

Article en En | MEDLINE | ID: mdl-15986357

RESUMEN

OBJECTIVE: To determine whether overexpression of BAFF can accelerate the development of systemic lupus erythematosus-associated end-organ disease in hosts with an underlying autoimmune diathesis. METHODS: We introduced a BAFF transgene (Tg) into autoimmune-prone B6.Sle1 and B6.Nba2 mice and evaluated these mice for serologic autoimmunity and renal pathology. RESULTS: B6.Sle1.BAFF and B6.Nba2.BAFF mice, but not non-Tg littermates, frequently developed severe glomerular pathology by 3 months of age. Age-matched B6.BAFF mice, despite renal Ig deposits and increases in B cells and Ig production similar to those in B6.Sle1.BAFF and B6.Nba2.BAFF mice, did not develop glomerular pathology. In B6.Sle1.BAFF and B6.Nba2.BAFF mice, severity of glomerular disease did not obligately correlate with circulating levels of IgG anti-chromatin and/or anti-double-stranded DNA antibodies or with amounts of these autoantibodies deposited in the kidneys. Even in mice with severe glomerular disease, renal tubulointerstitial infiltrates were very limited, and increased proteinuria was not detected. CONCLUSION: BAFF-driven effects on glomerular pathology may be mediated, at least in part, by autoantibodies with specificities other than chromatin and/or by autoantibody-independent means. There is an uncoupling of BAFF-driven precocious glomerular pathology from concomitant development of clinically apparent renal disease, strongly suggesting that BAFF overexpression works in concert with other factors to promote overt renal disease.

Asunto(s)

Expresión Génica; Predisposición Genética a la Enfermedad; Nefritis Lúpica/genética; Proteínas de la Membrana/genética; Factor de Necrosis Tumoral alfa/genética; Animales; Anticuerpos Antinucleares/inmunología; Factor Activador de Células B; Linfocitos B/patología; Cromatina/inmunología; ADN/inmunología; Modelos Animales de Enfermedad; Femenino; Inmunoglobulina G/inmunología; Glomérulos Renales/patología; Nefritis Lúpica/inmunología; Nefritis Lúpica/patología; Masculino; Proteínas de la Membrana/metabolismo; Ratones; Ratones Transgénicos; Bazo/patología; Linfocitos T/patología; Factores de Tiempo; Factor de Necrosis Tumoral alfa/metabolismo

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nefritis Lúpica / Expresión Génica / Factor de Necrosis Tumoral alfa / Predisposición Genética a la Enfermedad / Proteínas de la Membrana Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Arthritis Rheum Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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