Background/Purpose: To explore the pathogenic potential of lymphocytes in systemic sclerosis (SSc) and granulomatosis with polyangiitis (GPA), a humanized mouse model was generated by transferring human peripheral blood mononuclear cells (PBMC) into immunocompromised mice.

Methods: PBMC derived from patients with SSc and GPA were isolated, characerized by flow cytometry and infused into RAG2/IL2rg double- deficient mice. PBMC from healthy donors (HD) and from rituximab-treated SSc patients served as controls. Twelve weeks later, peripheral blood and tissues from recipient mice were collected and the latter examined by histology and immunohistology. Autoantibodies were analyzed in peripheral blood using ELISA or immunofluorescence assay on HEp-2 cells.

Results: Following transfer of PBMC derived from patients with SSc, total IgG and, in particular, SSc-related autoantibodies such as anti-AT1R, anti-ETAR antibodies and ANA were detected in recipient mice. In addition, infiltration of human lymphocytes was observed in multiple organs of recipient mice. In addition, infiltrations of human lymphocytes were observed in multiple organs of recipient mice, particularly lung, kindey and muscles. By contrast, although PBMC derived from HD or GPA patients also survived in recipient mice, no production of human autoantibodies and only marginal infiltration of human immune cells in lung, kidney, or muscles was found. Furthermore, transfer of PBMC derived from SSc patients predominantly featured an infiltration of human B cells in lung, kidneys and muscles, while no such cells were detected following transfer of PBMC derived from rituximab-treated SSc patients.

Conclusion: The humanized mouse model using adoptive transfer is indicative for intrinsic immune cell defects and argues for a pivotal role of B cells in the pathogenesis of SSc. It provides a powerful tool to study interstitial lung disease as so far under-recognized disease manifestations such as myositis and interstitial nephritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interstitial-lung-disease-kidney-inflammation-and-myositis-are-induced-by-transfer-of-pbmc-derived-from-systemic-sclerosis-patients-into-rag2-il2rg-mice/