Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms
Carregando...
Citações na Scopus
7
Tipo de produção
article
Data de publicação
2022
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Citação
FRONTIERS IN IMMUNOLOGY, v.13, article ID 933463, 19p, 2022
Resumo
Common variable immunodeficiency (CVID) is one of the inborn errors of immunity that have the greatest clinical impact. Rates of morbidity and mortality are higher in patients with CVID who develop liver disease than in those who do not. The main liver disorder in CVID is nodular regenerative hyperplasia (NRH), the cause of which remains unclear and for which there is as yet no treatment. The etiology of liver disease in CVID is determined by analyzing the liver injury and the associated conditions. The objective of this study was to compare CVID patients with and without liver-spleen axis abnormalities in terms of clinical characteristics, as well as to analyze liver and duodenal biopsies from those with portal hypertension (PH), to elucidate the pathophysiology of liver injury. Patients were divided into three groups: Those with liver disease/PH, those with isolated splenomegaly, and those without liver-spleen axis abnormalities. Clinical and biochemical data were collected. Among 141 CVID patients, 46 (32.6%) had liver disease/PH; 27 (19.1%) had isolated splenomegaly; and 68 (48.2%) had no liver-spleen axis abnormalities. Among the liver disease/PH group, patients, even those with mild or no biochemical changes, had clinical manifestations of PH, mainly splenomegaly, thrombocytopenia, and esophageal varices. Duodenal celiac pattern was found to correlate with PH (p < 0.001). We identified NRH in the livers of all patients with PH (n = 11). Lymphocytic infiltration into the duodenal mucosa also correlated with PH. Electron microscopy of liver biopsy specimens showed varying degrees of lymphocytic infiltration and hepatocyte degeneration, which is a probable mechanism of lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes. In comparison with the CVID patients without PH, those with PH were more likely to have lymphadenopathy (p < 0.001), elevated beta(2)-microglobulin (p < 0.001), low B-lymphocyte counts (p < 0.05), and low natural killer-lymphocyte counts (p < 0.05). In CVID patients, liver disease/PH is common and regular imaging follow-up is necessary. These patients have a distinct immunological phenotype that may predispose to liver and duodenal injury from lymphocyte-mediated cytotoxicity. Further studies could elucidate the cause of this immune-mediated mechanism and its treatment options.
Palavras-chave
inborn errors of immunity (IEI), primary immunodeficiency (PID), common variable immunodeficiency (CVID), portal hypertension, liver disease, nodular regenerative hyperplasia (NRH), enteropathy, duodenal celiac pattern
Referências
- Abbott JK, 2015, IMMUNOL ALLERGY CLIN, V35, P637, DOI 10.1016/j.iac.2015.07.009
- Abolhassani H, 2020, BLOOD, V135, P656, DOI 10.1182/blood.2019000929
- Aggarwal V, 2020, GENES DIS, V7, P26, DOI 10.1016/j.gendis.2019.10.002
- Al-Mukhaizeem KA, 2004, AM J HEMATOL, V75, P225, DOI 10.1002/ajh.20024
- Ameratunga R, 2020, IMMUNOL ALLERGY CLIN, V40, P403, DOI 10.1016/j.iac.2020.03.001
- Atalaia-Martins C, 2017, ACG CASE REP J, V4, DOI 10.14309/crj.2017.106
- Austin A, 2004, GUT, V53, P1032, DOI 10.1136/gut.2003.036806
- Azzu V, 2019, J ALLER CL IMM-PRACT, V7, P2484, DOI 10.1016/j.jaip.2019.04.016
- Baldassim MPM., 2014, THESIS FAC MED U SAO
- Bates CA, 2004, J ALLERGY CLIN IMMUN, V114, P415, DOI 10.1016/j.jaci.2004.05.057
- Bedossa P, 1996, HEPATOLOGY, V24, P289, DOI 10.1002/hep.510240201
- Biagi F, 2012, AM J CLIN PATHOL, V138, P185, DOI 10.1309/AJCPEIILH2C0WFYE
- BJERRUM OW, 1990, SCAND J IMMUNOL, V32, P233, DOI 10.1111/j.1365-3083.1990.tb02916.x
- Boileau J, 2011, J AUTOIMMUN, V36, P25, DOI 10.1016/j.jaut.2010.10.002
- Bonilla FA, 2016, J ALLER CL IMM-PRACT, V4, P38, DOI 10.1016/j.jaip.2015.07.025
- Brown LAK, 2017, REV MED VIROL, V27, DOI 10.1002/rmv.1926
- Chapel H, 2008, BLOOD, V112, P277, DOI 10.1182/blood-2007-11-124545
- Chawla Y, 2008, SEMIN LIVER DIS, V28, P270, DOI 10.1055/s-0028-1085095
- Chiou SJ, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22126330
- Crescenzi L, 2019, DIGEST LIVER DIS, V51, P1599, DOI 10.1016/j.dld.2019.05.016
- Crotty R, 2020, AM J SURG PATHOL, V44, P617, DOI 10.1097/PAS.0000000000001452
- Cunningham-Rundles C, 1999, CLIN IMMUNOL, V92, P34, DOI 10.1006/clim.1999.4725
- Daniels JA, 2007, AM J SURG PATHOL, V31, P1800, DOI 10.1097/PAS.0b013e3180cab60c
- Daniels JA, 2009, HUM PATHOL, V40, P484, DOI 10.1016/j.humpath.2008.09.008
- Fuss IJ, 2013, J CLIN IMMUNOL, V33, P748, DOI 10.1007/s10875-013-9873-6
- Gathmann B, 2014, J ALLERGY CLIN IMMUN, V134, P116, DOI 10.1016/j.jaci.2013.12.1077
- Goel A, 2013, INDIAN J MED RES, V137, P922
- Hartleb M, 2011, WORLD J GASTROENTERO, V17, P1400, DOI 10.3748/wjg.v17.i11.1400
- Islek A, 2021, ACTA GASTRO-ENT BELG, V84, P305, DOI 10.51821/84.2.305
- Jolles S, 2013, J ALLER CL IMM-PRACT, V1, P545, DOI 10.1016/j.jaip.2013.09.015
- Kaukinen K, 2002, GASTROENTEROLOGY, V122, P881, DOI 10.1053/gast.2002.32416
- Khodadad A, 2007, DIGEST DIS SCI, V52, P2977, DOI 10.1007/s10620-006-9736-6
- Kingham JGC, 1998, GUT, V42, P120, DOI 10.1136/gut.42.1.120
- Machado Márcio Martins, 2004, Radiol Bras, V37, P35, DOI 10.1590/S0100-39842004000100009
- Malamut G, 2008, J HEPATOL, V48, P74, DOI 10.1016/j.jhep.2007.08.011
- Malamut G, 2010, AM J GASTROENTEROL, V105, P2262, DOI 10.1038/ajg.2010.214
- Mannon PJ, 2006, GASTROENTEROLOGY, V131, P748, DOI 10.1053/j.gastro.2006.06.022
- Matsumoto T, 2000, LIVER, V20, P366, DOI 10.1034/j.1600-0676.2000.020005366.x
- Mayor PC, 2018, J ALLERGY CLIN IMMUN, V141, P1028, DOI 10.1016/j.jaci.2017.05.024
- Mechanic LJ, 1997, ANN INTERN MED, V127, P613, DOI 10.7326/0003-4819-127-8_Part_1-199710150-00005
- Mieli-Vergani G, 2018, NAT REV DIS PRIMERS, V4, DOI [10.1038/nrdp.2018.18, 10.1038/nrdp.2018.17]
- Mirzaagha F, 2010, DIGEST LIVER DIS, V42, P620, DOI 10.1016/j.dld.2010.02.006
- Morris JM, 2010, EUR J GASTROEN HEPAT, V22, P1001, DOI 10.1097/MEG.0b013e3283360021
- Myneedu K, 2021, ACG CASE REP J, V8, DOI 10.14309/crj.0000000000000547
- NABER AHJ, 1991, J HEPATOL, V12, P94, DOI 10.1016/0168-8278(91)90916-Y
- NORTH ME, 1991, CLIN EXP IMMUNOL, V86, P252
- Okabayashi A., 1983, IDIOPATHIC PORTAL HY, P197
- Oksenhendler E, 2008, CLIN INFECT DIS, V46, P1547, DOI 10.1086/587669
- Paquin-Proulx D, 2016, MEDICINE, V95, DOI 10.1097/MD.0000000000004304
- Pecoraro A, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.00338
- Pecoraro A, 2018, J CLIN IMMUNOL, V38, P67, DOI 10.1007/s10875-017-0461-z
- Pikkarainen S, 2019, AM J GASTROENTEROL, V114, P648, DOI 10.14309/ajg.0000000000000140
- Pollock G, 2020, ACG CASE REP J, V7, DOI 10.14309/crj.0000000000000467
- Pulvirenti F, 2014, J IMMUNOL RES, V2014, DOI 10.1155/2014/672458
- Reshamwala PA, 2006, HEPATOLOGY, V44, P7, DOI 10.1002/hep.21258
- Resnick ES, 2012, BLOOD, V119, P1650, DOI 10.1182/blood-2011-09-377945
- Robilotti E, 2015, CLIN MICROBIOL REV, V28, P134, DOI 10.1128/CMR.00075-14
- Sarin SK, 1998, DIGESTION, V59, P420, DOI 10.1159/000007502
- Schouten JNL, 2015, ORPHANET J RARE DIS, V10, DOI 10.1186/s13023-015-0288-8
- Schouten JNL, 2011, HEPATOLOGY, V54, P1071, DOI 10.1002/hep.24422
- Seve P, 2008, MEDICINE, V87, P177, DOI 10.1097/MD.0b013e31817a90ba
- Sharma BC, 2006, J GASTROEN HEPATOL, V21, P332, DOI 10.1111/j.1440-1746.2006.03296.x
- Shimamatsu K, 1997, HEPATOLOGY, V26, P343, DOI 10.1002/hep.510260214
- Sood A, 2014, WORLD J HEPATOL, V6, P55, DOI 10.4254/wjh.v6.i1.55
- Szablewski V, 2015, VIRCHOWS ARCH, V467, P733, DOI 10.1007/s00428-015-1862-0
- van Schewick CM, 2022, J CLIN IMMUNOL, V42, P46, DOI 10.1007/s10875-021-01104-5
- WANLESS IR, 1990, HEPATOLOGY, V11, P787, DOI 10.1002/hep.1840110512
- Ward C, 2008, CLIN EXP IMMUNOL, V153, P331, DOI 10.1111/j.1365-2249.2008.03711.x
- Warnatz K, 2002, BLOOD, V99, P1544, DOI 10.1182/blood.V99.5.1544
- Wehr C, 2008, BLOOD, V111, P77, DOI 10.1182/blood-2007-06-091744
- Woodward J, 2017, CLIN EXP IMMUNOL, V188, P363, DOI 10.1111/cei.12884
- Woodward JM, 2015, AM J GASTROENTEROL, V110, P320, DOI 10.1038/ajg.2014.432
- Yeh MM, 2006, AM J SURG PATHOL, V30, P727, DOI 10.1097/00000478-200606000-00008
- Yilmaz B, 2014, WORLD J GASTROENTERO, V20, P10916, DOI 10.3748/wjg.v20.i31.10916
- Ziol M, 2004, HUM PATHOL, V35, P1241, DOI 10.1016/j.humpath.2004.06.016
Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/06
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - LIM/19
Carregar mais Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/06
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - LIM/19