Faculty Collaboration Database

Rituximab and antimetabolite treatment of granulomatous and lymphocytic interstitial lung disease in common variable immunodeficiency. J Allergy Clin Immunol 2021 Feb;147(2):704-712.e17

Date

08/04/2020

Pubmed ID

32745555

DOI

10.1016/j.jaci.2020.07.021

Scopus ID

2-s2.0-85089870161 (requires institutional sign-in at Scopus site)   32 Citations

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.

Author List

Verbsky JW, Hintermeyer MK, Simpson PM, Feng M, Barbeau J, Rao N, Cool CD, Sosa-Lozano LA, Baruah D, Hammelev E, Busalacchi A, Rymaszewski A, Woodliff J, Chen S, Bausch-Jurken M, Routes JM

Authors

Amy Rymaszewski PhD Research Scientist I in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Luis Antonio Sosa Lozano MD Chief, Associate Professor in the Radiology department at Medical College of Wisconsin
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Azathioprine
Common Variable Immunodeficiency
Enzyme Inhibitors
Female
Humans
Immunosuppressive Agents
Lung Diseases, Interstitial
Male
Mycophenolic Acid
Respiratory Function Tests
Retrospective Studies
Rituximab
Young Adult