Acquired Pure Red Cell Aplasia and Acquired Amegakaryocytic Thrombocytopenia Associated With Clonal Expansion of T-Cell Large Granular Lymphocytes in a Patient With Lipopolysaccharide-responsive Beige-like Anchor (LRBA) Protein Deficiency

Abstract

Acquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura are rare in children. Similarly, clonal expansion of T-cell large granular lymphocytes is infrequently seen in pediatrics. Lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency is a recently described immunodeficiency syndrome that has been associated with inflammatory bowel disease and autoimmune phenomena such as Evans syndrome. Here, we describe a patient with LRBA deficiency who developed acquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura associated with expansion of clonal T-cell large granular lymphocytes. This has not been described in the literature previously and adds to the knowledge on the spectrum of manifestations of LRBA deficiency.

Case Report: Successful Avatrombopag Treatment for Two Cases of Anti-PD-1 Antibody-Induced Acquired Amegakaryocytic Thrombocytopenia

“…Although immune-related disorders are thought to be causative, the exact underlying pathogenesis remains unclear. The possible mechanisms associated with AAT involve activated T cells (T suppressor activated lymphocytes (Benedetti et al, 1994), T-cell large granular lymphocytes (Rajpurkar et al, 2019)), humoral immunity (anti-TPO antibody (Shiozaki et al, 2000), anti-c-Mpl antibody (Son et al, 2019)) or cytokine (Kimura et al, 1996)mediated disorders of megakaryocyte generation. For anti-PD-1/ PD-L1-induced AAT specifically, the underlying mechanism may be similar to those antitumor responses, which refer to the expansion of the T-cell repertoire.…”

Clonal T‐cell large granular lymphocyte proliferations in childhood and young adult immune dysregulation conditions

“…None of the cases had neutropenia as part of their spectrum in contrast to frequent association with T‐LGL leukemia in the literature. Three patients had chronic graft versus host disease (cGvHD), two Evans syndrome (ES), 10 and one case for each of the following conditions: common variable immunodeficiency disorder (CVID), severe combined immunodeficiency (SCID) with maternal engraftment who developed cytomegalovirus (CMV) infection following umbilical cord blood transplantation (UCBT) and later acute Epstein‐Barr virus (EBV) infection, 11 co‐existing Langerhans cell histiocytosis (LCH), and primary hemophagocytic lymphohistiocytosis (HLH), 12 autoimmune hemolytic anemia, chronic idiopathic thrombocytopenic purpura (cITP), Hodgkin lymphoma (HL), X‐linked lymphoproliferative disorder, Rosai‐Dorfman disease (RDD), acute EBV infection, acute parvovirus B19 infection, and paroxysmal nocturnal hemoglobinuria with history of treated severe aplastic anemia (Table 1). Pathophysiological processes involved in these cases included various combinations of inherited immune deficiency in four, acquired immune deficiency in five, lymphoproliferation in six, alloimmune reaction in three, autoimmune reaction in five, infection in four, inflammation in three, and malignancy in one case.…”

“…None of the cases had neutropenia as part of their spectrum in contrast to frequent association with T-LGL leukemia in the literature. Three patients had chronic graft versus host disease (cGvHD), two Evans syndrome (ES), 10…”

LGL Clonal Expansion and Unexplained Cytopenia: Two Clues Don’t Make an Evidence

“…In particular, inborn errors of immunity (IEIs) may confer susceptibility to chronic antigen exposure that lead to the clonal proliferation of lymphoid cells. T-LGL clonal expansions (sometimes fulfilling T-LGLL criteria) have been associated with germline mutations in ADA2 [ 91 ], CARD11 [ 92 ], and LRBA [ 93 ]. The recent discovery of TLR8 -GoF variants confirmed the importance of investigating genetic variants in IEIs, which are not necessarily defined based on their germline nature.…”