Immune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency
IntroductionAutoimmune disorders, IgA deficiency, and allergies seem to be common among individuals with 18q deletion syndrome [OMIM 601808]. We aimed to determine the prevalence, mechanism, and genetic background of autoimmunity, immune deficiency, and allergy in a cohort of patients with 18q delet...
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2021
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oai:doaj.org-article:27d4cd25ece548db9cc37e35506134122021-11-17T04:31:56ZImmune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency1664-322410.3389/fimmu.2021.742834https://doaj.org/article/27d4cd25ece548db9cc37e35506134122021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.742834/fullhttps://doaj.org/toc/1664-3224IntroductionAutoimmune disorders, IgA deficiency, and allergies seem to be common among individuals with 18q deletion syndrome [OMIM 601808]. We aimed to determine the prevalence, mechanism, and genetic background of autoimmunity, immune deficiency, and allergy in a cohort of patients with 18q deletions.Material and MethodsMedical registries and social media were used to recruit the patients. Microarray oligonucleotide comparative genomic hybridization (aCGH) (Agilent, Santa Clara, CA, USA) was performed in all patients to identify size and location of chromosome 18 deletion. Clinical evaluation and medical record collection were performed in each of the study participants. The history of autoimmune disorders, severe and/or recurrent infections, and symptoms of allergy were noted. Total immunoglobulin IgG, IgA, IgM, IgE, and IgG1-4 serum levels were measured using nephelometry and ELISA methods. Lymphocyte T subset phenotyping was performed in 24 subjects from 18q del cohort. To predict the most promising candidate genes, we used the ENDEAVOUR—a free web resource for gene prioritization.Results18q deletion was confirmed by means of array CGH analysis in 27 individuals, 15 (55.6%) females and 12 males, referred to the project by specialists in medical genetics, diabetology, or pediatric endocrinology between May 2015 and December 2019. The mean age at examination was 11.8 years (min–max: 4.0–33.5). Autoimmune disorders were present in 14/27 (51.8%) of the cohort. In eight of patients, symptoms of immune deficiency coexisted with autoimmunity. Allergy was reported in nine of 27 (33.4%) patients. Over 89% of patients presented with at list one type of immunoglobulin (IgA, IgM, IgG, IgE, and IgG1-4) deficiency and eight of 25 (32%) had abnormalities in at least two major immunoglobulin (IgG, IgA, IgM) measurements (CVID-like phenotype). Patients with 18q del exhibited a significantly decreased CD4, Treg FOXP3+, TregFOXP3+Helios+, and TemCD4 cell numbers in comparison with the control groups of 24 T1DM patients and 28 healthy controls.ConclusionsPatients with 18q deletions frequently suffer from autoimmune disorders, recurrent infections, and allergy due to immune dysregulation presenting with variable antibody deficiencies and T-regulatory cell deficiency (CD4+CD25+CD127lowFOXP3+). The spectrum of speculations regarding which gene might be responsible for such phenotype ranges from single gene haploinsufficiency to deletion of a cluster of immunogenes located distally to 18q21.Anna HogendorfMaciej ZielińskiMaria ConstantinouRobert ŚmigielJolanta WierzbaKrystyna WykaAnna WędrychowiczAnna Jakubiuk-TomaszukEdyta BudzynskaMalgorzata PiotrowiczBeata S. Lipska-ZiętkiewiczEwa KaczorowskaAgata CieślikowskaAnna Kutkowska-KaźmierczakJolanta Fijak-MoskalMonika KugaudoMałgorzata Kosińska-UrbańskaAgnieszka SzadkowskaMaciej BorowiecMaciej NiedźwieckiPiotr TrzonkowskiWojciech MłynarskiFrontiers Media S.A.article18q deletion syndromeimmune deficiencytype 1 diabetesautoimmune diseasesthyroiditisT regulatory cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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| topic |
18q deletion syndrome immune deficiency type 1 diabetes autoimmune diseases thyroiditis T regulatory cells Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
18q deletion syndrome immune deficiency type 1 diabetes autoimmune diseases thyroiditis T regulatory cells Immunologic diseases. Allergy RC581-607 Anna Hogendorf Maciej Zieliński Maria Constantinou Robert Śmigiel Jolanta Wierzba Krystyna Wyka Anna Wędrychowicz Anna Jakubiuk-Tomaszuk Edyta Budzynska Malgorzata Piotrowicz Beata S. Lipska-Ziętkiewicz Ewa Kaczorowska Agata Cieślikowska Anna Kutkowska-Kaźmierczak Jolanta Fijak-Moskal Monika Kugaudo Małgorzata Kosińska-Urbańska Agnieszka Szadkowska Maciej Borowiec Maciej Niedźwiecki Piotr Trzonkowski Wojciech Młynarski Immune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency |
| description |
IntroductionAutoimmune disorders, IgA deficiency, and allergies seem to be common among individuals with 18q deletion syndrome [OMIM 601808]. We aimed to determine the prevalence, mechanism, and genetic background of autoimmunity, immune deficiency, and allergy in a cohort of patients with 18q deletions.Material and MethodsMedical registries and social media were used to recruit the patients. Microarray oligonucleotide comparative genomic hybridization (aCGH) (Agilent, Santa Clara, CA, USA) was performed in all patients to identify size and location of chromosome 18 deletion. Clinical evaluation and medical record collection were performed in each of the study participants. The history of autoimmune disorders, severe and/or recurrent infections, and symptoms of allergy were noted. Total immunoglobulin IgG, IgA, IgM, IgE, and IgG1-4 serum levels were measured using nephelometry and ELISA methods. Lymphocyte T subset phenotyping was performed in 24 subjects from 18q del cohort. To predict the most promising candidate genes, we used the ENDEAVOUR—a free web resource for gene prioritization.Results18q deletion was confirmed by means of array CGH analysis in 27 individuals, 15 (55.6%) females and 12 males, referred to the project by specialists in medical genetics, diabetology, or pediatric endocrinology between May 2015 and December 2019. The mean age at examination was 11.8 years (min–max: 4.0–33.5). Autoimmune disorders were present in 14/27 (51.8%) of the cohort. In eight of patients, symptoms of immune deficiency coexisted with autoimmunity. Allergy was reported in nine of 27 (33.4%) patients. Over 89% of patients presented with at list one type of immunoglobulin (IgA, IgM, IgG, IgE, and IgG1-4) deficiency and eight of 25 (32%) had abnormalities in at least two major immunoglobulin (IgG, IgA, IgM) measurements (CVID-like phenotype). Patients with 18q del exhibited a significantly decreased CD4, Treg FOXP3+, TregFOXP3+Helios+, and TemCD4 cell numbers in comparison with the control groups of 24 T1DM patients and 28 healthy controls.ConclusionsPatients with 18q deletions frequently suffer from autoimmune disorders, recurrent infections, and allergy due to immune dysregulation presenting with variable antibody deficiencies and T-regulatory cell deficiency (CD4+CD25+CD127lowFOXP3+). The spectrum of speculations regarding which gene might be responsible for such phenotype ranges from single gene haploinsufficiency to deletion of a cluster of immunogenes located distally to 18q21. |
| format |
article |
| author |
Anna Hogendorf Maciej Zieliński Maria Constantinou Robert Śmigiel Jolanta Wierzba Krystyna Wyka Anna Wędrychowicz Anna Jakubiuk-Tomaszuk Edyta Budzynska Malgorzata Piotrowicz Beata S. Lipska-Ziętkiewicz Ewa Kaczorowska Agata Cieślikowska Anna Kutkowska-Kaźmierczak Jolanta Fijak-Moskal Monika Kugaudo Małgorzata Kosińska-Urbańska Agnieszka Szadkowska Maciej Borowiec Maciej Niedźwiecki Piotr Trzonkowski Wojciech Młynarski |
| author_facet |
Anna Hogendorf Maciej Zieliński Maria Constantinou Robert Śmigiel Jolanta Wierzba Krystyna Wyka Anna Wędrychowicz Anna Jakubiuk-Tomaszuk Edyta Budzynska Malgorzata Piotrowicz Beata S. Lipska-Ziętkiewicz Ewa Kaczorowska Agata Cieślikowska Anna Kutkowska-Kaźmierczak Jolanta Fijak-Moskal Monika Kugaudo Małgorzata Kosińska-Urbańska Agnieszka Szadkowska Maciej Borowiec Maciej Niedźwiecki Piotr Trzonkowski Wojciech Młynarski |
| author_sort |
Anna Hogendorf |
| title |
Immune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency |
| title_short |
Immune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency |
| title_full |
Immune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency |
| title_fullStr |
Immune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency |
| title_full_unstemmed |
Immune Dysregulation in Patients With Chromosome 18q Deletions—Searching for Putative Loci for Autoimmunity and Immunodeficiency |
| title_sort |
immune dysregulation in patients with chromosome 18q deletions—searching for putative loci for autoimmunity and immunodeficiency |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/27d4cd25ece548db9cc37e3550613412 |
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