PMID- 32655575
OWN - NLM
STAT- MEDLINE
DCOM- 20210420
LR  - 20210420
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Congenital Hemolytic Anemias: Is There a Role for the Immune System?
PG  - 1309
LID - 10.3389/fimmu.2020.01309 [doi]
LID - 1309
AB  - Congenital hemolytic anemias (CHAs) are a heterogeneous group of rare hereditary 
      conditions including defects of erythrocyte membrane proteins, red cell enzymes, 
      and disorders due to defective erythropoiesis. They are characterized by variable 
      degree of anemia, chronic extravascular hemolysis, reduced erythrocyte life span, 
      splenomegaly, jaundice, biliary lithiasis, and iron overload. Although few data 
      are reported on the role of the immune system in CHAs, several immune-mediated 
      mechanisms may be involved in the pathogenesis of these rare diseases. We 
      reported in ~60% of patients with hereditary spherocytosis (HS), the presence of 
      naturally-occurring autoantibodies (NAbs) directed against different membrane 
      proteins (alpha- and beta-spectrin, band 3, and dematin). Positive HS subjects showed a 
      more hemolytic pattern and NAbs were more evident in aged erythrocytes. The 
      latter is in line with the function of NAbs in the opsonization of 
      damaged/senescent erythrocytes and their consequent removal in the spleen. 
      Splenectomy, usually performed to reduce erythrocyte catheresis and improve Hb 
      levels, has different efficacy in various CHAs. Median Hb increase is 3 g/dL in 
      HS, 1.6-1.8 g/dL in pyruvate kinase deficiency (PKD), and 1 g/dL in congenital 
      dyserythropoietic anemias (CDA) type II. Consistently with clinical severity, 
      splenectomy is performed in 20% of HS, 45% of CDAII, and in 60% of PKD patients. 
      Importantly, sepsis and thrombotic events have been registered, particularly in 
      PKD with a frequency of ~7% for both. Furthermore, we analyzed the role of 
      pro-inflammatory cytokines and found that interleukin 10 and interferon gamma, and to 
      a lesser extent interleukin 6, were increased in all CHAs compared with controls. 
      Moreover, CDAII and enzymatic defects showed increased tumor necrosis factor-alpha 
      and reduced interleukin 17. Finally, we reported that iron overload occurred in 
      31% of patients with membrane defects, in ~60% of CDAII cases, and in up to 82% 
      of PKD patients (defined by MRI liver iron concentration >4 mg Fe/gdw). Hepcidin 
      was slightly increased in CHAs compared with controls and positively correlated 
      with ferritin and with the inflammatory cytokines interleukin 6 and interferon gamma. 
      Overall the results suggest the existence of a vicious circle between chronic 
      hemolysis, inflammatory response, bone marrow dyserythropoiesis, and iron 
      overload.
CI  - Copyright (c) 2020 Zaninoni, Fermo, Vercellati, Marcello, Barcellini and Bianchi.
FAU - Zaninoni, Anna
AU  - Zaninoni A
AD  - UOS Fisiopatologia delle Anemie, UOC Ematologia, Fondazione IRCCS Ca' Granda 
      Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Fermo, Elisa
AU  - Fermo E
AD  - UOS Fisiopatologia delle Anemie, UOC Ematologia, Fondazione IRCCS Ca' Granda 
      Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Vercellati, Cristina
AU  - Vercellati C
AD  - UOS Fisiopatologia delle Anemie, UOC Ematologia, Fondazione IRCCS Ca' Granda 
      Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Marcello, Anna Paola
AU  - Marcello AP
AD  - UOS Fisiopatologia delle Anemie, UOC Ematologia, Fondazione IRCCS Ca' Granda 
      Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Barcellini, Wilma
AU  - Barcellini W
AD  - UOS Fisiopatologia delle Anemie, UOC Ematologia, Fondazione IRCCS Ca' Granda 
      Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Bianchi, Paola
AU  - Bianchi P
AD  - UOS Fisiopatologia delle Anemie, UOC Ematologia, Fondazione IRCCS Ca' Granda 
      Ospedale Maggiore Policlinico, Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200623
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies)
RN  - 0 (Cytokines)
RN  - 11096-26-7 (Erythropoietin)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Anemia, Hemolytic, Congenital/*immunology
MH  - Animals
MH  - Antibodies/immunology
MH  - Cytokines/immunology
MH  - Erythropoietin/immunology
MH  - Humans
MH  - Immune System
MH  - Iron/immunology
MH  - Spleen/immunology/surgery
MH  - Splenectomy
PMC - PMC7324678
OTO - NOTNLM
OT  - congenital hemolytic anemias
OT  - cytokines
OT  - inflammation
OT  - iron overload
OT  - naturally occurring antibodies
OT  - splenectomy
EDAT- 2020/07/14 06:00
MHDA- 2021/04/21 06:00
PMCR- 2020/01/01
CRDT- 2020/07/14 06:00
PHST- 2020/02/17 00:00 [received]
PHST- 2020/05/22 00:00 [accepted]
PHST- 2020/07/14 06:00 [entrez]
PHST- 2020/07/14 06:00 [pubmed]
PHST- 2021/04/21 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01309 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jun 23;11:1309. doi: 10.3389/fimmu.2020.01309. eCollection 
      2020.