Traffic jam within lymphocytes: A clinician’s perspective

Abstract

With the discovery of novel diseases and pathways, as well as a new outlook on certain existing diseases, cellular trafficking disorders attract a great deal of interest and focus. Understanding the function of genes and their products in protein and lipid synthesis, cargo sorting, packaging, and delivery has allowed us to appreciate the intricate pathophysiology of these biological processes at the molecular level and the multi-system disease manifestations of these disorders. This article focuses primarily on lymphocyte intracellular trafficking diseases from a clinician’s perspective. Familial hemophagocytic lymphohistiocytosis is the prototypical disease of abnormal vesicular transport in the lymphocytes. In this review, we highlight other mechanisms involved in cellular trafficking, including membrane contact sites, autophagy, and abnormalities of cytoskeletal structures affecting the immune cell function, based on a newer classification system, along with management aspects of these conditions.

HLH Syndrome in a Community Hospital: The Challenge of an Early Diagnosis

“…It is characterized by cytotoxic T cell (CTL) dysfunction, coupled with uninhibited macrophage activity. 1 Malfunction of cytotoxic T cells result in the overproduction of cytokines and, eventually, tissue damage. Familial or genetic HLH is caused by an underlying genetic defect or a complication of other genetic syndromes.…”

“…Familial or genetic HLH is caused by an underlying genetic defect or a complication of other genetic syndromes. 1 , 2 Secondary HLH or syndromic HLH in children is caused by infections (most common), malignancies, and autoimmune or autoinflammatory conditions in the absence of a known genetic predisposition to HLH. 1 , 2 Recently, a case of HLH resulting from gene therapy was reported, possibly secondary to the Adeno-associated virus (AAV) vector used in this case, adding another potential risk to gene therapy.…”

“… 1 , 2 Secondary HLH or syndromic HLH in children is caused by infections (most common), malignancies, and autoimmune or autoinflammatory conditions in the absence of a known genetic predisposition to HLH. 1 , 2 Recently, a case of HLH resulting from gene therapy was reported, possibly secondary to the Adeno-associated virus (AAV) vector used in this case, adding another potential risk to gene therapy. 3 HLH has an estimated prevalence of 1 in 100,000 children 4 and familial HLH has a reported incidence of 1.2 in 1,000,000 children.…”