James W Verbsky1, Mary K Hintermeyer2, Pippa M Simpson3, Mingen Feng3, Jody Barbeau3, Nagarjun Rao4, Carlyne D Cool5, Luis A Sosa-Lozano6, Dhiraj Baruah7, Erin Hammelev8, Alyssa Busalacchi8, Amy Rymaszewski8, Jeff Woodliff8, Shaoying Chen9, Mary Bausch-Jurken8, John M Routes10. 1. Division of Pediatric Rheumatology, Medical College Wisconsin, Milwaukee, Wis; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis. 2. Asthma, Allergy and Clinical Immunology, Children's Wisconsin, Milwaukee, Wis. 3. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis; Department of Quantitative Health Sciences, Medical College Wisconsin, Milwaukee, Wis. 4. Department of Pathology, Aurora Clinical Laboratories/Great Lakes Pathologists, Aurora West Allis Medical Center, West Allis, Wis. 5. Department of Pathology and Division of Pulmonary and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colo; National Jewish Health, Denver, Colo. 6. Division of Diagnostic Radiology, Medical College of Wisconsin, Milwaukee, Wis. 7. Division of Thoracic Radiology, Medical University of South Carolina, Charleston, SC. 8. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis; Division of Asthma, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, Wis. 9. Division of Pediatric Rheumatology, Medical College Wisconsin, Milwaukee, Wis; Division of Asthma, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, Wis. 10. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis; Division of Asthma, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, Wis. Electronic address: jroutes@mcw.edu.
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.
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.
Authors: Astrid C van Stigt; Willem A Dik; Lieke S J Kamphuis; Bas M Smits; Joris M van Montfrans; P Martin van Hagen; Virgil A S H Dalm; Hanna IJspeert Journal: Front Immunol Date: 2020-12-17 Impact factor: 7.561
Authors: Olivia A C Lamers; Bas M Smits; Helen Louisa Leavis; Godelieve J de Bree; Charlotte Cunningham-Rundles; Virgil A S H Dalm; Hsi-En Ho; John R Hurst; Hanna IJspeert; Sabine M P J Prevaes; Alex Robinson; Astrid C van Stigt; Suzanne Terheggen-Lagro; Annick A J M van de Ven; Klaus Warnatz; Janneke H H M van de Wijgert; Joris van Montfrans Journal: Front Immunol Date: 2021-04-15 Impact factor: 7.561