Rituximab Monotherapy for Common Variable Immune Deficiency-Associated Granulomatous-Lymphocytic Interstitial Lung Disease

Abstract

Patients with common variable immunodeficiency (CVID) can develop granulomatouslymphocytic interstitial lung disease (GLILD), which is associated with increased morbidity and mortality. Treating GLILD is a significant challenge because it is rare and can be pathologically heterogeneous. Here we describe two cases of patients with CVID-associated GLILD with biopsies demonstrating loosely organized tertiary lymphoid structures (TLSs). Based on the pivotal role that B cells play in TLS initiation and maintenance, we hypothesized that using rituximab monotherapy for B-cell depletion alone would be sufficient for the disruption of the pathologic process underlying GLILD. These two cases demonstrate that adapting a strategy of B cell depletion monotherapy may be effective in TLS-associated conditions such as GLILD.

Granulomatous lymphocytic interstitial lung disease: limiting immunosuppressive therapy—a single‐centre experience

“…The largest reported series targeted T and B lymphocytes with combination therapy of rituximab and azathioprine (or mycophenolate) [13]. Other authors have hypothesized that B cells are required to maintain tertiary lymphoid structures central to inflammation in GLILD and reported success with rituximab monotherapy [14,15].…”

From infections to autoimmunity: Diagnostic challenges in common variable immunodeficiency

“…Center experiences vary and even the natural history of GLILD is not well described. Patients are often put on corticosteroids with other immunosuppressive therapies and rituximab as a second line treatment[ 35 , 44 ]. The STILPAD study is a multi-center observational study looking at the effect of various treatments on interstitial lung disease (ILD) in patients with CVID and ILD that had been diagnosed by a chest CT scan[ 45 ].…”

A double-edged sword

“…CVID-associated interstitial lung disease is challenging and covers a broad spectrum of overlapping histological and radiological patterns ( e.g. nonspecific interstitial pneumonia, organising pneumonia, granulomatous disease) [ 7 , 8 , 11 , 12 ]. This heterogeneity has led to the implementation of the “umbrella” definition of GLILD, which is defined as a distinct clinico–radio–pathological lung disease occurring in patients with CVID, associated with lymphocytic infiltrates and/or granulomas in the lung and in whom other conditions have been considered and where possible excluded.…”