Anti-desmoglein-1 levels as predictor of prednisolone tapering in pemphigus vulgaris patients treated with rituximab

Balighi, Kamran; Sakhi, Roya-Sadaat; Daneshpazhooh, Maryam; Mahmoudi, Hamidreza; Teimourpour, Amir; Tavakolpour, Soheil

doi:10.1111/dth.12671

Cited by 13 publications

(14 citation statements)

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“…Thus, it is imperative to identify and use readily available biomarkers that allow early relapse detection and recognition of patients at high risk of relapse [7]. Several biomarkers for predicting clinical relapse in PV have been described so far, including anti-desmoglein 1 and 3 autoantibodies [8], CD4 cell count, CD19+ B cell repopulation in the peripheral blood [9], and Th2 cytokines [10]. These biomarkers are not routinely used as they are not widely available, expensive, and their processing is timeconsuming.…”

Section: Introductionmentioning

confidence: 99%

Hematological Inflammatory Markers in Patients with Pemphigus Vulgaris

et al. 2021

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Background: Emerging evidence indicates that several hematological markers can be used to evaluate treatment response, prediction, and early relapse detection in different inflammatory conditions. This study aimed to investigate the correlation between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, platelet-to-neutrophil ratio, mean platelet volume, and disease activity in patients with pemphigus vulgaris. Methods: Fifty-six patients (20 men, 36 women; mean age 54 ± 14 years) diagnosed with pemphigus vulgaris were included in this retrospective study. Patients were divided into those treated and not treated with rituximab (groups 1 and 2), and into those who did and did not develop relapse (groups 3 and 4). The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, platelet-to-neutrophil ratio and mean platelet volume were evaluated at the time of diagnosis, remission, and relapse. The relationship between each marker and disease stage was analyzed using the Wilcoxon rank-sum test for pairwise comparisons. Results: The neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio showed a positive correlation with disease activity, while the platelet-to-neutrophil ratio and mean platelet volume showed a negative correlation. The neutrophil-to-lymphocyte ratio significantly decreased in remission (p < 0.001) and significantly increased in relapse (p < 0.01). The platelet-to-lymphocyte ratio significantly decreased in remission (p < 0.001) and showed no significant change in relapse. The platelet-to-neutrophil ratio significantly increased in remission (p < 0.001) and significantly decreased at relapse (p < 0.001). The mean platelet volume significantly increased in remission (p < 0.001) and decreased non-significantly at relapse. A more significant decrease in the neutrophil-to-lymphocyte ratio in remission was found in patients not treated with rituximab. No significant differences were observed between patients who developed relapse and those who did not. Conclusion: Our results suggest that the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, platelet-to-neutrophil ratio, and mean platelet volume can be useful markers for monitoring treatment response, while the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio can also assist in detecting early relapse.

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Section: Introductionmentioning

confidence: 99%

Hematological Inflammatory Markers in Patients with Pemphigus Vulgaris

et al. 2021

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“…CD4+ T cells' count, levels of anti-Dsg1/3 antibodies, and disease duration had been reported as potential (bio) markers for prediction of clinical response in pemphigus patients. 16,17 The present study was therefore conducted to investigate the expression of aforementioned critical immune system-related genes, including CTLA4, PDCD1, TNFSF13B, FCGR3A, EBI3, IL9, IL21, and IL22 genes in pemphigus patients compared to healthy controls, as well as monitoring the changes of these genes in patients 3 months after RTX infusion.…”

Section: Introductionmentioning

confidence: 99%

“…In spite of using RTX for both PV and PF patients since 16 years, 15 and its promising results with a relatively safe profile, demand for finding (bio)markers for prediction of treatment response is still felt. CD4+ T cells' count, levels of anti‐Dsg1/3 antibodies, and disease duration had been reported as potential (bio)markers for prediction of clinical response in pemphigus patients 16,17 …”

Section: Introductionmentioning

confidence: 99%

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

Tavakolpour

Mahmoudi

Karami

et al. 2020

Dermatologic Therapy

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Pemphigus is a rare group of autoimmune diseases, which its exact molecular pathogenesis and therapeutic biomarkers remained unknown. In this regard the expressions of eight immune-related genes was evalualted in pemphigus patients. Forty-six pemphigus patients, either new case or on minimal therapy, were recruited. The expressions of IL22, IL9, IL21, EBI3, TNFSF13B, FCGR3A, CTLA4, and PDCD1 genes were analyzed at baseline, compared with 32 healthy controls, and their changes were monitored 3 months after rituximab (RTX) therapy through Reverse Transcriptase Real-time PCR (RT-Real-time PCR). Except of IL21, which was similar in both groups, expressions of other genes were significantly lower in patients compared with the controls (P-value <.05). PDCD1, EBI3, IL21, and IL22 genes were significantly overexpressed three months following RTX administration (P-value <.05). Higher prednisolone dosage and PDAI-score were positively correlated with CTLA4 and FCGR3A expressions after 3 months, respectively (P-value = .019 and .048, respectively). Anti-desmoglein 1 (Dsg 1) titer and its positivity at baseline were associated with TNFSF13B expression, FCGR3A expressions, and the PDAI-score. Our results suggest the possible involvement of some gene expressions in pemphigus immunopathogenesis, which could be affected by RTX therapy and also might be used as prognostic biomarkers.

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“…Furthermore, Balighi et al. found better outcomes in patients treated with rituximab within 6 months of diagnosis ( 12 ). In our study, patients achieving complete remission had a mean disease duration of 67 months prior to rituximab therapy, against 82 months in those not achieving complete remission.…”

Section: Discussionmentioning

confidence: 99%

Rituximab - Progress but Still Not a Final Resolution for Pemphigus Patients: Clinical Report From a Single Center Study

2022

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Pemphigus is a rare autoimmune disease characterized by the production of pathogenic autoantibodies against desmosomal adhesion proteins, desmoglein 1 and 3. The pathophysiological process leads to the development of blisters and erosions on mucosal and/or skin surfaces as the main clinical manifestation of the disease. Rituximab emerged as the first-line therapeutic option for pemphigus due to its ability to induce remission by depleting peripheral B lymphocytes. Our aim was to assess the efficacy of rituximab in the treatment of patients in Croatia. A single-center, retrospective study was conducted on 19 patients treated with rituximab following a rheumatoid arthritis dosing protocol between October 2015 and March 2021, with a mean follow-up of 24.1 months. After the first rituximab cycle, two patients achieved complete remission off therapy (10.5%), and six patients achieved complete remission on minimal therapy (31.6%). Partial remission was observed among ten patients (52.6%). Eight patients (44.4%) relapsed after the first rituximab cycle. The mean relapse time was 21 months. Seven patients received two rituximab cycles, and three patients received three cycles. Overall, 13 out of 19 patients experienced complete remission at some point during the study, while there were no non-responders after the rituximab treatment. No statistically significant associations were observed between age, sex, type of disease involvement and clinical remission, either on or off therapy. A steady decrease in anti-desmoglein 1 and anti-desmoglein 3 levels was measured among all patients following rituximab treatment. One patient experienced a treatment-related adverse event of infectious etiology (cellulitis). One patient died following the first rituximab cycle, with the cause of death likely not to be associated with the treatment. Rituximab is an effective disease-modifying agent in the treatment of pemphigus with the main benefit of reducing corticosteroid exposure and steroid-related side effects among pemphigus patients. However, a feature of rituximab therapy is high relapse rates and the need for repeated treatment cycles to achieve complete remission. Developing an optimal protocol for rituximab treatment and finding suitable markers for predicting relapse will improve the management of pemphigus patients.

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Anti-desmoglein-1 levels as predictor of prednisolone tapering in pemphigus vulgaris patients treated with rituximab

Cited by 13 publications

References 7 publications

Hematological Inflammatory Markers in Patients with Pemphigus Vulgaris

Hematological Inflammatory Markers in Patients with Pemphigus Vulgaris

Investigating expression pattern of eight immune‐related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy

Rituximab - Progress but Still Not a Final Resolution for Pemphigus Patients: Clinical Report From a Single Center Study

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