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Anti‐CXCL13 and anti‐TNF α combination therapy in a mouse model of systemic lupus erythematosus
Author(s) -
Gardner Debra Bryce,
Bassiri Ashlyn,
Bugelski Peter,
Sarisky Robert,
Liang Bailin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.473
Subject(s) - cxcl13 , germinal center , spleen , b cell , medicine , lymph , inflammation , immunology , pathogenesis , autoantibody , antibody , pathology , chemokine , chemokine receptor
CXCL13 is a potent chemoattractant critical for B cell migration and follicle formation in lymph node and spleen, and it is required for the development of most lymph nodes and Peyer's patches. CXCL13 is elevated in ectopic B cell follicles formed in the inflamed tissues of multiple chronic inflammatory diseases, and plays an important role in maintaining inflammation. Our study investigated the effect of treatment with anti‐ mouse CXCL13 alone and in combination with anti‐mouse TNFa in a mouse model of spontaneous Systemic Lupus Erythematosus (SLE). NZB/W F1 mice treated with anti‐mCXCL13 and anti‐mTNFa mAbs show significantly decreased B cell proliferation. Anti‐mCXCL13/anti‐mTNFa mAb treatment also decreased serum anti‐dsDNA autoantibody levels, as compared to the anti‐mTNFa treated group. Anti‐mCXCL13/anti‐ mTNFa treatment significantly decreased kidney pathology by reducing lymphocyte infiltration and glomerular inflammation The combination treatment also significantly reduced urine/protein creatinine ratios. In addition, anti‐mCXCL13/anti‐mTNFa mAbs treatment suppressed germinal center formation in the spleen. This result demonstrates a crucial role for CXCL13 and TNFa in the pathogenesis of SLE.