Interstitial lung disease in patients with common variable immunodeficiency disorders: several different pathologies?

• Published in: Clinical and experimental immunology Vol. 198; no. 2; pp. 212 - 223
• Main Authors: Patel, S., Anzilotti, C., Lucas, M., Moore, N., Chapel, H.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.11.2019; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biopsy; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Child; clinical outcomes; Common variable immunodeficiency; Common Variable Immunodeficiency - immunology; Common Variable Immunodeficiency - pathology; common variable immunodeficiency disorder; Computed tomography; Databases, Factual; Female; Fibrosis; Follicles; Follow-Up Studies; Germinal centers; Granuloma, Respiratory Tract - immunology; Granuloma, Respiratory Tract - pathology; Histology; Humans; interstitial lung diseases; Longitudinal studies; Lung - immunology; Lung - pathology; Lung diseases; Lung Diseases, Interstitial - immunology; Lung Diseases, Interstitial - pathology; Lymphocytes; Lymphocytes T; Male; Middle Aged; Nodules; Organs; Original; Prognosis; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - pathology; several pathologies; standardization of data; clinical outcomes; several pathologies; standardization of data; interstitial lung diseases; common variable immunodeficiency disorder
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13343

Summary Various reports of disease‐related lung pathologies in common variable immunodeficiency disorder (CVID) patients have been published, with differing histological and high‐resolution computed tomography (HRCT) findings. Data were extracted from the validated Oxford Primary Immune Deficiencies  Database (PID) database (1986–2016) on adult, sporadic CVID patients with suspected interstitial lung disease (ILD). Histology of lung biopsies was studied in relation to length of follow‐up, clinical outcomes, HRCT findings and chest symptoms, to look for evidence for different pathological processes. Twenty‐nine CVID patients with lung histology and/or radiological evidence of ILD were followed. After exclusions, lung biopsies from 16 patients were reanalysed for ILD. There were no well‐formed granulomata, even though 10 patients had systemic, biopsy‐proven granulomata in other organs. Lymphocytic infiltration without recognizable histological pattern was the most common finding, usually with another feature. On immunochemistry (n = 5), lymphocytic infiltration was due to T cells (CD4 or CD8). Only one patient showed B cell follicles with germinal centres. Interstitial inflammation was common; only four of 11 such biopsies also showed interstitial fibrosis. Outcomes were variable and not related to histology, suggesting possible different pathologies. The frequent nodules on HRCT were not correlated with histology, as there were no well‐formed granulomata. Five patients were asymptomatic, so it is essential for all patients to undergo HRCT, and to biopsy if abnormal HRCT findings are seen. Internationally standardized pathology and immunochemical data are needed for longitudinal studies to determine the precise pathologies and prognoses in this severe complication of CVIDs, so that appropriate therapies may be found. Differing histological and HRCT findings in interstitial lung disease in patients with common variable immune deficiencies (CVID) suggest various pathologies. There were no well‐formed granulomata in such lung biopsies, despite biopsy‐proven granulomata elsewhere. Non‐organised T lymphocytic infiltration was common, usually with another feature; only one patient showed B cell follicles with germinal centres. Outcomes were variable and not related to histology or HRCT findings. Five patients were asymptomatic, so it is essential to biopsy patients with abnormal HRCT findings. Internationally standardised pathology definitions are essential if aetiologies of CVID interstitial lung disease, and therefore appropriate treatments, are to be found.