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4. Targeting Multiple End Organs in Lupus and Other Systemic Rheumatic Diseases by Inhibiting Bruton’s Tyrosine Kinase.

Author

Yong Du, Ling Lei, Huihua Ding, Yanping Chen, Pathak, Simanta, Hicks, John, Tran, Phuongthy T., Minghua Wu, Chang, Betty, Wirtz, Uwe, and Mohan, Chandra

Abstract

Bruton tyrosine kinase (Btk) plays a vital role in activating and differentiating B-cells and regulating signaling in myeloid cells. Indeed, the potential use of Btk inhibitors in preventing lupus has been reported. Here, we extend these observations to 4 additional models of end-organ inflammation: (a) BWF1 lupus nephritis mice, (b) anti-GBM nephritis, (c) bleomycin-induced systemic sclerosis like skin disease, and (d) bleomycin-induced lung disease. In agreement with the previous studies, BTK inhibitor (BTKB66) treatment was effective in treating lupus nephritis in terms of reducing renal damage both functionally and histologically, accompanied by significant decrease in proteinuria. Both low-dose and high-dose BTKB66 profoundly blocked renal disease in the anti-GBM nephritis model, with efficacy that was comparable to that seen with dexamethasone. This study provides the first evidence that BTK inhibition has both therapeutic and preventative effects in bleomycin-induced SSc-like disease, in terms of reducing skin thickness, fibrosis, collagen deposition, and inflammation. Likewise, significantly lower lung inflammatory cell infiltration was observed after treatment with BTKB66. Therapeutic benefit was associated with lower numbers of macrophages, proliferating macrophages and activated T-cells in the respective injured organs. The observation that these immune cells play key roles in driving end organ inflammation in multiple systemic rheumatic diseases have broad implications for the use of BTKB66 in managing patients with systemic rheumatic diseases where multiple end organs are afflicted, including lupus and systemic sclerosis. [ABSTRACT FROM AUTHOR]

Published
2022
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5. Fatty Acid Amide Hydrolase Regulates Peripheral B Cell Receptor Revision, Polyreactivity, and B1 Cells in Lupus

Author

Pathak, Simanta, primary, Kumar, Kirthi Raman, additional, Kanta, Hasna, additional, Carr-Johnson, Ferdicia, additional, Han, Jie, additional, Bashmakov, Anna, additional, Faure, Lionel, additional, Ding, Huihua, additional, Vanarsa, Kamala, additional, Khan, Shaheen, additional, Li, Quan-Zhen, additional, Chapman, Kent, additional, Wakeland, Edward K., additional, and Mohan, Chandra, additional

Published
2016
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6. BANK1 transgenic mice exhibit lupus-associated B cell phenotypes

Author

Pathak, Simanta, Guo, Yuyuan, Ding, Huihua, Du, Yong, Min, Soyoun, Vanarsa, Kamala, Li, Quanzhen, Kozyrev, Sergey, Alarcon-Riquelme, Marta, Mohan, Chandra, Pathak, Simanta, Guo, Yuyuan, Ding, Huihua, Du, Yong, Min, Soyoun, Vanarsa, Kamala, Li, Quanzhen, Kozyrev, Sergey, Alarcon-Riquelme, Marta, and Mohan, Chandra

Published
2015

15. Expressed sequence tags from feline uterine library

Author

Pathak, Simanta and Kapil, Sanjay

Abstract

Partial nucleotide sequences of 634 cDNAs randomly isolated from a feline uterine cDNA library (Stratagene) were determined by single pass sequencing. Homology search of the sequences to the non-redundant nucleotide databases revealed that 83% of the cDNAs matched registered feline or non-feline genes. Based on the gene identifications, these genes were predicted to be related with immunological, biochemical and regulatory functions in cats. Interestingly, the rest 17% of the cDNAs did not show homology to gene or EST sequence present in the nucleotide and protein databases, suggesting that these cDNAs include novel genes expressed only in the Felidae. This large scale sequencing of uterine cDNA will provide a useful molecular source for research not only towards health and disease conditions in cats but also in different fields of science where genetic information from cats will be of interest.

Published
2006
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