Rituximab and antimetabolite treatment of granulomatous and lymphocytic interstitial lung disease in common variable immunodeficiency

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. Our aim was to determine whether rituximab with azathioprine or mycophenolate mofetil improves the high-r...

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Published in:	Journal of allergy and clinical immunology Vol. 147; no. 2; pp. 704 - 712.e17
Main Authors:	Verbsky, James W., Hintermeyer, Mary K., Simpson, Pippa M., Feng, Mingen, Barbeau, Jody, Rao, Nagarjun, Cool, Carlyne D., Sosa-Lozano, Luis A., Baruah, Dhiraj, Hammelev, Erin, Busalacchi, Alyssa, Rymaszewski, Amy, Woodliff, Jeff, Chen, Shaoying, Bausch-Jurken, Mary, Routes, John M.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-02-2021
Subjects:	Common variable immunodeficiency granulomatous and lymphocytic interstitial lung disease primary immunodeficiency MCW VATS Common variable immunodeficiency MMF CNS PID TLC IQR GLILD CT CVID FVC DLCO granulomatous and lymphocytic interstitial lung disease primary immunodeficiency CTLA4 HRCT LFT NK PFT
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Summary:	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. 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. 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. 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. Immunosuppressive therapy improved the radiographic abnormalities and pulmonary function of patients with GLILD. A majority of patients had sustained remissions.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0091-6749 1097-6825
DOI:	10.1016/j.jaci.2020.07.021