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Rituximab and antimetabolite treatment of granulomatous and lymphocytic interstitial lung disease in common variable immunodeficiency - 04/02/21

Doi : 10.1016/j.jaci.2020.07.021 
James W. Verbsky, MD a, b, Mary K. Hintermeyer, RN, APNP c, Pippa M. Simpson, PhD b, d, Mingen Feng, MS b, d, Jody Barbeau, BS b, d, Nagarjun Rao, MD e, Carlyne D. Cool, MD f, g, Luis A. Sosa-Lozano, MD h, Dhiraj Baruah, MD i, Erin Hammelev, MS b, j, Alyssa Busalacchi, BS b, j, Amy Rymaszewski, PhD b, j, Jeff Woodliff, PhD b, j, Shaoying Chen, MD a, j, Mary Bausch-Jurken, PhD b, j, John M. Routes, MD b, j,
a Division of Pediatric Rheumatology, Medical College Wisconsin, Milwaukee, Wis 
b Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis 
c Asthma, Allergy and Clinical Immunology, Children’s Wisconsin, Milwaukee, Wis 
d Department of Quantitative Health Sciences, Medical College Wisconsin, Milwaukee, Wis 
e Department of Pathology, Aurora Clinical Laboratories/Great Lakes Pathologists, Aurora West Allis Medical Center, West Allis, Wis 
f Department of Pathology and Division of Pulmonary and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colo 
g National Jewish Health, Denver, Colo 
h Division of Diagnostic Radiology, Medical College of Wisconsin, Milwaukee, Wis 
i Division of Thoracic Radiology, Medical University of South Carolina, Charleston, SC 
j Division of Asthma, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, Wis 

Corresponding author: John Routes, MD, Medical College of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI 53226-4874.Medical College of Wisconsin9000 W Wisconsin AveMilwaukeeWI53226-4874

Abstract

Background

Granulomatous and lymphocytic interstitial lung disease (GLILD) is a life-threatening complication in patients with common variable immunodeficiency (CVID), but the optimal treatment is unknown.

Objective

Our aim was to determine whether rituximab with azathioprine or mycophenolate mofetil improves the high-resolution computed tomography (HRCT) chest scans and/or pulmonary function test results in patients with CVID and GLILD.

Methods

A retrospective chart review of clinical and laboratory data on 39 patients with CVID and GLILD who completed immunosuppressive therapy was performed. Chest HRCT scans, performed before therapy and after the conclusion of therapy, were blinded, randomized, and scored independently by 2 radiologists. Differences between pretreatment and posttreatment HRCT scan scores, pulmonary function test results, and lymphocyte subsets were analyzed. Whole exome sequencing was performed on all patients.

Results

Immunosuppressive therapy improved patients' HRCT scan scores (P < .0001), forced vital capacity (P = .0017), FEV1 (P = .037), and total lung capacity (P = .013) but not their lung carbon monoxide diffusion capacity (P = .12). Nine patients relapsed and 6 completed retreatment, with 5 of 6 of these patients (83%) having improved HRCT scan scores (P = .063). Relapse was associated with an increased number of B cells (P = .016) and activated CD4 T cells (P = .016). Four patients (10%) had pneumonia while undergoing active treatment, and 2 patients (5%) died after completion of therapy. Eight patients (21%) had a damaging mutation in a gene known to predispose (TNFRSF13B [n = 3]) or cause a CVID-like primary immunodeficiency (CTLA4 [n = 2], KMT2D [n = 2], or BIRC4 [n = 1]). Immunosuppression improved the HRCT scan scores in patients with (P = .0078) and without (P < .0001) a damaging mutation.

Conclusions

Immunosuppressive therapy improved the radiographic abnormalities and pulmonary function of patients with GLILD. A majority of patients had sustained remissions.

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Key words : Common variable immunodeficiency, granulomatous and lymphocytic interstitial lung disease, primary immunodeficiency

Abbreviations used : CNS, CT, CTLA4, CVID, DLCO, FVC, GLILD, HRCT, IQR, LFT, MCW, MMF, NK, PFT, PID, TLC, VATS


Plan


 Supported by the Jeffrey Modell Foundation, Children's Research Institute, and the Department of Pediatrics, Medical College of Wisconsin.
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.


© 2020  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 147 - N° 2

P. 704 - février 2021 Retour au numéro
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