Implication of B lymphocytes in the pathogenesis of ANCA-associated vasculitides

Dumoitier, N.; Terrier, Benjamin; London, Jonathan; Lofek, Sébastien; Mouthon, Luc

doi:10.1016/j.autrev.2015.06.008

Cited by 49 publications

(24 citation statements)

References 123 publications

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“…Rituximab (RTX), an anti-human CD20 antibody has been shown to be highly effective in deleting expanded B-clones and improving MC syndrome [5][6][7][8][9][10][11][12][13] and other autoimmune conditions [14][15][16][17] in a majority of cases. However, no data are presently available on the very longterm efficacy and safety after RTX administration in MC, nor on the possible indications of maintenance therapy.…”

Section: Introductionmentioning

confidence: 99%

Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study

Roccatello

Sciascia²,

Baldovino³

et al. 2016

Am J Nephrol

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Background: In a prospective, single-center open study, we evaluated the very long-term effects of rituximab (RTX) administered to patients with severe mixed cryoglobulinemia (MC). Methods: RTX was administered to 31 patients with MC (type II in 29 cases and type III in 2) with diffuse membranoproliferative glomerulonephritis (16 cases), peripheral neuropathy (26) and large skin ulcers (7). All but 4 patients had serum anti-hepatitis C virus antibodies. RTX was administered at a dose of 375 mg/m², according to a ‘4 + 2' protocol (days 1, 8, 15 and 22 plus 1 dose 1 and 2 months later). No other immunosuppressive drugs were added. Response was evaluated over a very long-term follow-up (mean 72.47 months, range 30-148). Results: Complete remission of pretreatment active manifestations was observed in all cases of purpuric lesions and non-healing vasculitic ulcers, and in 80% of the peripheral neuropathies. Cryoglobulinemic nephropathy significantly improved during follow-up, starting from the 2nd month after RTX (serum creatinine from 2.1 ± 1.7 to 1.5 ± 1.6 mg/dl, p ≤ 0.05; 24-hour proteinuria from 2.3 ± 2.1 to 0.9 ± 1.9 g/24 h, p ≤ 0.05). Improvement of cryoglobulinemic serological hallmarks, such as cryocrit and low complement C4, were observed. No clinically relevant side effects were recorded. Re-induction with RTX was carried out in 9 relapsed patients after a mean of 31.1 months (12-54), again with beneficial effects. The survival rate was 75% at 6 years and the probability of remaining symptom-free for 10 years without any therapy was of about 60% after a single ‘4 + 2' infusion cycle, while the probability of living symptom-free 5 years after relapsing was 80% if given the same treatment. Conclusion: In this open, prospective study, RTX appeared to be very effective and safe in the treatment of the most severe cases of MC.

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Section: Introductionmentioning

confidence: 99%

Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study

Roccatello

Sciascia²,

Baldovino³

et al. 2016

Am J Nephrol

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“…Finally, 282 cases of biopsy-proven leukocytoclastic vasculitis were discussed with a focus on direct immunofluorescence detection of immunoglobulin and complement deposition at the blood vessel wall. Their findings support immune complex deposition in the blood vessel wall being relevant to determine underlying conditions related to this disease [18,19]. The meeting ended up with many clinical and basic issues being discussed and with a clear agreement that the 11th meeting on autoimmunity should be a wider platform for new issues to be raised, and move on toward further scientific achievements.…”

Section: Immune-mediated Diseases and Mechanisms Of Inflammationmentioning

confidence: 90%

Biomarkers and Pathogenic Mechanisms in Autoimmunity

2016

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“…Broadly, it is postulated that the proliferation of B cells contributes to a chronic inflammatory-like state through expression and inhibition of various cytokines [4], contributing to the development of localized ischemia. Even though the patient was asymptomatic for a long period of time prior to her diagnosis, her underlying lymphoma likely contributed to the localized inflammatory factors compressing the mesenteric vessels and changing the nature of the gastric mucosa.…”

Section: Discussionmentioning

confidence: 99%

Follicular B Cell Lymphoma with Accompanying Ischemic Gastritis Completely Resolved by Rituximab

2017

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Patient: Female, 89Final Diagnosis: Follicular B-cell lymphoma with accompanying ischemic gastritis completely resolved by rituximabSymptoms: Nausea • vomitingMedication: —Clinical Procedure: —Specialty: OncologyObjective:Rare diseaseBackground:Follicular B cell lymphomas account for a significant portion of all newly diagnosed non-Hodgkin’s lymphomas. While involvement can be varied, the most common extranodal presentation is within the gastrointestinal tract beyond the stomach. In addition, the stomach has a diffuse multivessel vascular supply, which decreases the likelihood of developing ischemic gastritis.Case Report:An 89-year-old woman with history of diabetes, deep venous thromboembolism, and hypertension was referred due to a newly diagnosed retroperitoneal mass. Biopsy of a left para-aortic node was consistent with low-grade follicular B cell lymphoma. Following mainstream treatment guidelines, rituximab was administered. Approximately 12 hours later, the patient presented to the Emergency Department with intractable vomiting and nausea. After admission, an esophagogastroduodenoscopy (EGD) revealed extensive ischemic gastritis. Due to recurrent ascites requiring frequent paracenteses, and the clinical aggressiveness of the patient’s underlying lymphoma, a second dose of rituximab was administered with concurrent initiation of total parenteral nutrition. Approximately 1 week later, the patient underwent a repeat EGD for quality of life planning while in hospice. The repeat EGD revealed resolved ischemic gastritis. Her diet was advanced and she was subsequently discharged home.Conclusions:Rituximab alone shows promise in treating extensive follicular B cell lymphoma complicated by ischemic gastritis, which has not been previously reported in the literature.

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Implication of B lymphocytes in the pathogenesis of ANCA-associated vasculitides

Cited by 49 publications

References 123 publications

Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study

Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study

Biomarkers and Pathogenic Mechanisms in Autoimmunity

Follicular B Cell Lymphoma with Accompanying Ischemic Gastritis Completely Resolved by Rituximab

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