Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism

Abstract

Hypopigmentation disorders that are associated with immunodeficiency feature both partial albinism of hair, skin and eyes together with leukocyte defects. These disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS) and MAPBP-interacting protein deficiency syndromes. These are heterogeneous autosomal recessive conditions in which the causal genes encode proteins with specific roles in the biogenesis, function and trafficking of secretory lysosomes. In certain specialized cells, these organelles serve as a storage compartment. Impaired secretion of specific effector proteins from that intracellular compartment affects biological activities. In particular, these intracellular granules are essential constituents of melanocytes, platelets, granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus, abnormalities affect pigmentation, primary hemostasis, blood cell counts and lymphocyte cytotoxic activity against microbial pathogens. Among eight genetically distinct types of HPS, only type 2 is characterized by immunodeficiency. Recently, a new subtype, HPS9, was defined in patients presenting with immunodeficiency and oculocutaneous albinism, associated with mutations in the pallidin-encoding gene, PLDN.Hypopigmentation together with recurrent childhood bacterial or viral infections suggests syndromic albinism. T and NK cell cytotoxicity are generally impaired in patients with these disorders. Specific clinical and biochemical phenotypes can allow differential diagnoses among these disorders before molecular testing. Ocular symptoms, including nystagmus, that are usually evident at birth, are common in patients with HPS2 or CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP) deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term complication of CHS, but is uncommon in other syndromic albinism. Chronic neutropenia is a feature of HPS2 and MAPBPIP-deficiency syndrome, whereas it is usually transient in CHS and GS2. In every patient, an accurate diagnosis is required for prompt and appropriate treatment, particularly in patients who develop HLH or in whom bone marrow transplant is required. This review describes the molecular and pathogenetic mechanisms of these diseases, focusing on clinical and biochemical aspects that allow early differential diagnosis.

Snapin promotes HIV ‐1 transmission from dendritic cells by dampening TLR 8 signaling

“…Mutations in genes encoding proteins of the BLOC‐1 complex are defective in inbred mouse strains that serve as models of HPS, a rare autosomal‐recessive disorder characterized by hypopigmentation and platelet storage pool deficiency and also associated with immunodeficiencies (Dotta et al , 2013). The HPS protein AP‐3 has already been shown to affect the late stages of the HIV‐1 replication cycle, with the matrix region of Gag interacting directly with the delta subunit of the AP‐3 complex to promote Gag trafficking in human embryonic kidney 293T cells (Dong et al , 2005).…”

Chediak Higashi syndrome presenting in accelerated phase: a case report and literature review

“…Staphylococcus aureus and beta-hemolytic Streptococcus are the predominant organisms. Viral and fungal infections, however, have also been described 13 . Increased susceptibility to recurrent infections is attributed to defects in T-cell cytotoxicity and natural killer function and defects in granulocyte chemotaxis and bactericidal activity.…”

“…Increased susceptibility to recurrent infections is attributed to defects in T-cell cytotoxicity and natural killer function and defects in granulocyte chemotaxis and bactericidal activity. 13 The accelerated phase is observed in 85% of individuals and can occur at any age, including shortly after birth or within several years. Clinical manifestations include fever, lymphadenopathy, hepatosplenomegaly, anemia, neutropenia, thrombocytopenia, and neurological abnormalities.…”

Hemofagocitinė limfohistiocitozė: literatūros apžvalga

“…Svarbiausi jų yra 2-o tipo Griscelli sindromas (GS-2) (įvyksta RAB27A Santrumpos: FHL -šeiminė HLH; CHS -Chediak-Hisgashi sindromas; GS-2 -Griscelli sindromas, 2 tipas; XLP -su X chromosoma susijęs limfoproliferacinis sindromas; HPS-2 -Hermansky-Pudlak sindromas, 2 tipas; SCID -sunkus kombinuotas imunodeficitas; ITK -interleukino-2 indukuojama T limfocitų kinazė (10). geno mutacijos, simptomai -hipoalbinizmas, imunodeficitas ir / ar neurologinė simptomatika), Chediak-Higashi sindromas (CHS) (CHS1/ LYST geno mutacija, simptomai -dalinis akių ir odos albinizmas, neutrofilų defektai, neutropenija ir neurologinis pakenkimas), Hermansky-Pudlak sindromas (HPS) (HPS-2 tipas -pasireiškia akių ir odos albinizmas, trombocitų agregacijos sutrikimas ir neseniai atrasta sąsaja tarp imunodeficito ir albinizmo, apibūdinama HPS-9 tipu) (6,11). Šių heterogeninių, autosominiu recesyviniu būdu paveldimų būklių mutacijos įvyksta genuose, koduojančiuose proteinus, svarbius lizosomų biogenezei, funkcionavimui bei tranzitinei funkcijai (6,11).…”