Iguratimod reduces B-cell secretion of immunoglobulin to play a protective role in interstitial lung disease

Abstract Background: Several cases of chemotherapy-induced interstitial lung disease (ILD) or pneumonitis have been reported in recent years in patients with lymphoma. The potential roles of rituximab (R) and granulocyte colony stimulating factor (GCSF), agents more commonly used in recent years, are suggested. Objective: We wanted to determine the prevalence of ILD and identify risk factors in patients with diffuse large B-cell lymphoma (DLCL) who received cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP)-based chemotherapy. Methods: Selection criteria included newly diagnosed DLCL patients treated at our institution from 2000–2006 who received CHOP with or without R and had at least 3 serial CT or PET/CT scans during chemotherapy. ILD was defined as new bilateral interstitial pulmonary infiltrates not likely representing fluid overload or fibrosis. One radiologist blinded to clinical data reviewed all imaging studies. Results: Out of a total of 174 new cases of DLCL, 73 met our study criteria. Reasons for exclusion included no chemotherapy (45), <3 imaging studies (46), and non-CHOP-based chemotherapy (10). Among the 73 study patients, 52 (71%) received R in addition to CHOP. Eleven (15.1%) patients developed ILD, all in the subgroup that received RCHOP (P = 0.027). Most occurred between cycles 2 and 4 of RCHOP (81.8%) and persisted until after completion of chemotherapy (63.6%). Nine (81.8%) patients with ILD were asymptomatic and never required treatment or delay of RCHOP. The remaining 2 patients became symptomatic (1 hospitalized), were empirically treated for atypical pneumonia with clinical recovery, and had delay of RCHOP. All patients received the intended number of courses of RCHOP. Univariate analysis of potential ILD risk factors among those who received RCHOP showed a trend with the subgroup that either had GCSF or cardiopulmonary disease (P = 0.09). Multivariate analysis using a two-variable model suggests that the use of GCSF or presence of cardiopulmonary disease (P = 0.065) and a high (3–5) international prognostic index score (P = 0.13) need further investigation as risk factors. Conclusions: In our cohort of DLCL patients receiving CHOP-based chemotherapy, ILD was common and significantly associated with the use of R. While most cases were asymptomatic, self-limited, and did not require delay of chemotherapy, more serious presentation could occur. The mechanism of ILD is unknown and requires further investigation.

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Elevated serum B‐cell activating factor levels in patients with dermatomyositis: Association with interstitial lung disease

The Journal of Dermatology ◽

10.1111/1346-8138.15117 ◽

2019 ◽

Vol 46 (12) ◽

pp. 1190-1196

Author(s):

Takashi Matsushita ◽

Tadahiro Kobayashi ◽

Miyu Kano ◽

Yasuhito Hamaguchi ◽

Kazuhiko Takehara

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

B Cell ◽

Elevated Serum ◽

B Cell Activating Factor

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Intravascular Large B-cell Lymphoma Presenting as Interstitial Lung Disease

Nihon Naika Gakkai Zasshi ◽

10.2169/naika.96.2783 ◽

2007 ◽

Vol 96 (12) ◽

pp. 2783-2785 ◽

Cited By ~ 2

Author(s):

Ai Fujiwara ◽

Taichi Azuma ◽

Jun Yamanouchi ◽

Hiroshi Narumi ◽

Yoshihiro Yakushijin ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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B cell infiltration in systemic sclerosis–associated interstitial lung disease

Arthritis & Rheumatism ◽

10.1002/art.22847 ◽

2007 ◽

Vol 56 (9) ◽

pp. 3167-3168 ◽

Cited By ~ 92

Author(s):

Robert Lafyatis ◽

Carl O'Hara ◽

Carol A. Feghali-Bostwick ◽

Eric Matteson

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

B Cell ◽

Cell Infiltration

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POS0858 POTENTIAL EFFICACY PREDICTORS OF ANTI-B-CELL THERAPY IN THE PATIENTS WITH SYSTEMIC SCLEROSIS ASSOCIATED WITH INTERSTITIAL LUNG DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2313 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 683.2-684

Author(s):

O. Koneva ◽

L. P. Ananyeva ◽

L. Garzanova ◽

O. Desinova ◽

O. Ovsyannikova ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Correlation Analysis ◽

Cell Therapy ◽

Lung Disease ◽

B Cell ◽

Disease Duration ◽

Potential Efficacy ◽

Group A ◽

Group B

Background:Rituximab (RTM) is considered as a promising therapeutic agent for treatment of With Interstitial Lung Disease (ILD) in the patients with systemic sclerosis (SSc). However, the limited number of RTM-treated patients, considerably varying dose regimens, cumulative doses and observation periods, lack of data on potential predictors of RTM therapy response do not allow univocal conclusions on RTM efficacy or definitive recommendations on RTM use in the patients with SSc.Objectives:The study of potential efficacy predictors of anti-B-cell therapy in the patients with SSc associated with ILD.Methods:90 patients with SSc-ILD verified by multispiral computed tomography were enrolled to the study and received RTM therapy for 12-42 months at cumulative dose 2.9±1.1 grams (disease duration 5.9±4.8 years, diffused/limited SSc 1.3/1, average age 47 ± 13.6 years, females 83%). All patients received low or moderate dose glucocorticoids. 45 patients received RTM in addition to immunosuppressive therapy (cyclophosphamide and mycophenolate mofetil) because of inadequate efficacy of immunosuppressants. After evaluation of FVC trends in the patients receiving RTM the overall study population was divided into two patient groups for the analysis: group A (n=35) comprised the patients with ≥10% FVC increase (disease duration 6.1±5.8 years, diffused/limited SSc 1,3/1, average age 50±12 years, females 86%, cumulative RTM dose 3.2±1.24 grams), and group B (n=11) comprised the patients with ≥5% FVC decrease (disease duration 5.2±4, diffused/limited SSc 0.8/1, average age 43±16, females 72%, cumulative RTM dose 2.5±0.99 grams). Subsequently correlation analysis was made to clarify the association between delta FVC and a number of clinical (age, gender, duration and form of SSc, modified skin count, presence of gastroesophageal reflux, mPAP, SSc activity (EScSG, points), cumulative RTM dose, immunosuppressive therapy) and laboratory parameters (ESR, ANA-НЕР-2, a-Scl-70, CRP, B cell count).Results:In the overall patient population RTM therapy was associated with significant FVC increase from 77.0±19.9 % to 84.7±20.9% (р=0.000000), with median FVC increment 6.6% [0;14.1].In group A FVC increased from 75.3±19.9 to 94.3±20.4) (р=0.000000), with median FVC increment 16.3 [12.6; 24.7].In group B FVC decreased from 82.5 ±23.2 to 72,3±19.4 (р=0,000176), with median FVC decrement 10.4% [-13.4; -6].Correlation analysis in groups A and B showed significant association of between delta FVC and the patient age (R=0.36), cumulative RTM dose (R=0.34) and EScSG during the last examination (1.2±.,0 and 3.1±1.4 in groups A and B, respectively; R=-0.42).No significant correlation between delta FVC and any other tested parameters was found.Conclusion:Therefore, older patients who received the cumulative rituximab dose more than 3 grams with suppressed SSc activity achieved greater FVC increase at the background of therapy. These data allow to consider the above parameters as potential predictors of response to anti-B-cell therapy in the patients with SSc-ILD.Disclosure of Interests:None declared

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THU0420 An extent of interstitial lung disease is a potential predictor of response to a-b-cell therapy in the patients with ssc

10.1136/annrheumdis-2018-eular.4543 ◽

2018 ◽

Author(s):

O. Koneva ◽

O. Desinova ◽

O. Ovasyannikova ◽

L. Garzanova ◽

M. Starovoytova ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Cell Therapy ◽

Lung Disease ◽

B Cell ◽

Potential Predictor

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Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease

Frontiers in Immunology ◽

10.3389/fimmu.2020.616832 ◽

2021 ◽

Vol 11 ◽

Author(s):

David Friedmann ◽

Susanne Unger ◽

Baerbel Keller ◽

Mirzokhid Rakhmanov ◽

Sigune Goldacker ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Interstitial Lung Disease ◽

Bronchoalveolar Lavage ◽

Lung Disease ◽

B Cell ◽

Cell Subset ◽

Immune Dysregulation

BackgroundAbout 20% of patients with common variable immunodeficiency (CVID) suffer from interstitial lung disease (ILD) as part of a systemic immune dysregulation. Current understanding suggests a role of B cells in the pathogenesis based on histology and increased levels of BAFF and IgM associated with active disease corroborated by several reports which demonstrate the successful use of rituximab in CVID-ILD. It is debated whether histological confirmation by biopsy or even video-assisted thoracoscopy is required and currently not investigated whether less invasive methods like a bronchoalveolar lavage (BAL) might provide an informative diagnostic tool.ObjectiveTo gain insight into potential immune mechanisms underlying granulomatous and lymphocytic interstitial lung disease (GLILD) and to define biomarkers for progressive ILD by characterizing the phenotype of B- and T-cell populations and cytokine profiles in BAL fluid (BALF) of CVID-ILD compared to sarcoidosis patients and healthy donors (HD).MethodsSixty-four CVID, six sarcoidosis, and 25 HD BALF samples were analyzed by flow cytometric profiling of B- and T-cells and for cytokines by ELISA and Multiplexing LASER Bead technology.ResultsBoth sarcoidosis and CVID-ILD are characterized by a predominantly T-cell mediated lymphocytosis in the BALF. There is an increase in T follicular helper (TFH)-like memory and decrease of regulatory T cells in CVID-ILD BALF. This TFH-like cell subset is clearly skewed toward TH1 cells in CVID-ILD. In contrast to sarcoidosis, CVID-ILD BALF contains a higher percentage of B cells comprising mostly CD21low B cells, but less class-switched memory B cells. BALF analysis showed increased levels of APRIL, CXCL10, and IL-17.ConclusionUnlike in sarcoidosis, B cells are expanded in BALF of CVID-ILD patients. This is associated with an expansion of TFH- and TPH-like cells and an increase in APRIL potentially supporting B-cell survival and differentiation and proinflammatory cytokines reflecting not only the previously described TH1 profile seen in CVID patients with secondary immune dysregulation. Thus, the analysis of BALF might be of diagnostic value not only in the diagnosis of CVID-ILD, but also in the evaluation of the activity of the disease and in determining potential treatment targets confirming the prominent role of B-cell targeted strategies.

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