Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency

Abstract

Primary immunodeficiency (PID) with immune dysregulation may present with early onset gastrointestinal autoimmune disorders. When gastrointestinal autoimmunity is associated with multiple extraintestinal immune system dysfunction the diagnosis of PID is straightforward. However, with the advent of next generation sequencing technologies, genetic defects in PID genes have been increasingly recognized even when a single or no extraintestinal signs of immune dysregulation are present. A genetic diagnosis is especially important considering the expanding armamentarium of therapies designed to inhibit specific molecular pathways. We describe a boy with early-onset severe, refractory autoimmune gastritis and biallelic mutations in the LRBA gene causing a premature STOP-codon who was successfully treated with CTLA4-Ig, abatacept, with long term clinical and endoscopic remission. The case underscores the importance to consider a monogenetic defect in early onset autoimmune disorders, since the availability of targeted treatments may significantly improve patient prognosis.

Keywords: LRBA deficiency; abatacept; autoimmune gastritis; case report; inflammatory bowel disease; lymphoproliferation; primary immumunodeficiencies.

Figure 1

Retroverted view of the proximal stomach, showing diffuse mucosal congestion and hyperemia with discrete amounts of mucus and bleeding.

Figure 2

Endoscopic view of the distal stomach showing diffuse mucosal congestion, hyperemia and erosions.

Figure 3

Endoscopic view of the large curvature of the stomach showing a normal mucosa with decreased gastric folds and increased visibility of the mucosal vascular pattern.

Figure 4

Mechanism of action of abatacept in LRBA deficiency. (A) normal immune responses are based on a balance between stimulatory signals (interaction of CD28 on T lymphocytes with CD80 and CD86 on antigen presenting cells) and inhibitory signals (block of CD80 and CD86 by CTLA4 expressed by lymphocytes). This balance is particularly critical in regulatory T cells, which can express higher levels of CTLA4. (B) biallelic mutations in LRBA result in impaired recycling of CTLA4 to the membrane, leading to reduced expression of the protein and increased lymphocyte stimulation. The addition of abatacept (CTLA4-Ig) partially compensates the lack of cell-bound CTLA4. T, T cell; APC, Antigen Presenting Cell.