420. Anti-SLAMF7 therapy in a case of refractory IgG4-associated sclerosing mesenteritis
Creators: name: Lamprecht1, Peter
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Presentation of Case</strong>: A 67-year-old woman was referred to our department due to persistent abdominal pain of the umbilical and hypogastric region and intermittent diarrhoea. Her history was otherwise unremarkable apart from a cholecystectomy 15 years before. <strong>Diagnostic Testing:</strong> Chest radiograph, gastroscopy and coloscopy showed normal findings. Abdominal CT imaging disclosed soft-tissues masses encasing the superior mesenteric artery (SMA). Retroperitoneal fibrosis or (peri-)aortitis was not evident. Laboratory testing showed normal values for ESR, CRP, WBC, DBC, creatinine, ALT, AST, ANA, ENA, RF, ANCA, serum-IgG4, and urine analysis. Histopathological findings from a CT-guided biopsy showed a fibro-inflammatory lesion rich in spindle cells with interspersed lymphoplasmacytic infiltrates containing 70 IgG+ and 45 IgG4+ cells per high-power field. The IgG4/IgG ratio was &gt;0.6. Moreover, obliterative phlebitis and storiform fibrosis were found. <strong>Differential &amp; Final Diagnosis:</strong> Differential diagnoses of abdominal soft-tissue masses comprise various disorders affecting the mesentery and peritoneum and inflammatory retroperitoneal conditions such as retroperitoneal fibrosis, abdominal aortitis and periaortitis. IgG4-related disease (IgG4-RD) is associated with SM and inflammatory retroperitoneal disorders in 10 – 50% of the cases. No further organ involvement is found in most IgG4-associated SM cases. In our patient, the diagnosis was based on characteristic abdominal imaging and histopathology findings indicative of IgG4-associated SM [2]. <strong>Discussion of Management</strong>: Following diagnosis, glucocorticoid therapy was started. The patient`s disease however remained refractory to glucocorticoid and subsequent thalidomide, rituximab and cyclophosphamide therapy. Abdominal CT imaging showed a progress of soft-tissue mass-forming lesions obstructing the SMA. Since cytotoxic CD4+SLAMF7+ innate-like T-cells and plasmablasts are considered to be key drivers of IgG4-RD pathology [1], the patient was switched to a course of monoclonal anti-SLAMF7 antibody (elotuzumab) therapy (cumulative dose 6 g i.v. in 12 weeks). We used flow cytometry to follow peripheral blood cell profiles at baseline and subsequently until week 12 under elotuzumab therapy. During this period, we observed a decrease of SLAMF7+ cell frequencies within the circulating neutrophil and monocyte populations and an increase within the lymphocyte population. We found an expansion of SLAMF7 expressing CD4+CD28-CD27- innate-like T-cells and CD4+CD8+ “double-positive” T-cells, which remained unaffected by therapy. An increase in the frequency of CD3-CD56+ NK cells and CD3+CD56+ NKT cells under elotuzumab therapy suggests an immunological response [3]. The patient remained in stable disease for 6 months. <strong>Conclusions</strong>: Refractory IgG4-associated SM remains a therapeutic challenge. Elotuzumab could be a therapeutic option in IgG4-RD and is currently tested in a two-part multi-centre clinical trial in the USA (NCT04918147). <strong>Disclosures:</strong> None.