The genetics of IgA deficiency : a ‛two-disease’ approach
Selective IgA deficiency (IgAD) is the most common primary immunodeficiency disorder in Caucasians with a prevalence of approximately 1:600 in the general population. It is defined as serum IgA levels below or equal to 0.07 g/l with normal serum levels of IgM and IgG above the age of 4. Most IgAD in...
| Main Author: | |
|---|---|
| Format: | Doctoral or Postdoctoral Thesis |
| Language: | English |
| Published: |
Inst för laboratoriemedicin / Dept of Laboratory Medicine
2015
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/10616/41823 |
| id |
ftkarolinskainst:oai:openarchive.ki.se:10616/41823 |
|---|---|
| record_format |
openpolar |
| institution |
Open Polar |
| collection |
Karolinska Institutet: Publications |
| op_collection_id |
ftkarolinskainst |
| language |
English |
| description |
Selective IgA deficiency (IgAD) is the most common primary immunodeficiency disorder in Caucasians with a prevalence of approximately 1:600 in the general population. It is defined as serum IgA levels below or equal to 0.07 g/l with normal serum levels of IgM and IgG above the age of 4. Most IgAD individuals are asymptomatic, however, one-third suffer from respiratory and gastrointestinal infections and concomitant autoimmune diseases. IgAD is associated with several classical autoimmune disorders including Graves’ disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD) and potentially rheumatoid arthritis and myasthenia gravis (MG). As more than 95% of patients with GD are positive for thyrotropin-receptor autoantibody (TRAb), we thus investigated the prevalence of IgAD in TRAb-seropositive individuals both in Sweden and Iceland and showed that the prevalence of IgAD in the Swedish cohort is significantly higher than expected in the general population. TRAb- seropositivity is also common among IgAD individuals in both cohorts, suggesting a predisposition to GD (Paper I). There is a markedly increased prevalence of IgAD among adults with CD. It is therefore important to validate the IgG class antibody tests for screening CD in IgAD adults. IgG anti tissue transglutaminase (anti-tTG) and anti deamidated gliadin peptides (anti-DGP) antibodies were determined in our IgAD cohort with suspected CD. IgG anti-tTG seems to be a reliable marker for CD in IgAD adults whereas the diagnostic specificity of IgG anti-DGP appears to be lower. We also found that high levels of IgG antibodies against both tTG and DGP were frequently found in IgAD adults despite adhering to a gluten free diet (Paper II). We subsequently screened IgAD among patients with SLE and T1D in different ethnical populations and the observed higher prevalence of IgAD was consistent with previous publications (Paper III). IgAD is reported to be strongly associated with the MHC region, especially the HLA- A1, B8, DR3, DQ2 ... |
| format |
Doctoral or Postdoctoral Thesis |
| author |
Wang, Ning |
| spellingShingle |
Wang, Ning The genetics of IgA deficiency : a ‛two-disease’ approach |
| author_facet |
Wang, Ning |
| author_sort |
Wang, Ning |
| title |
The genetics of IgA deficiency : a ‛two-disease’ approach |
| title_short |
The genetics of IgA deficiency : a ‛two-disease’ approach |
| title_full |
The genetics of IgA deficiency : a ‛two-disease’ approach |
| title_fullStr |
The genetics of IgA deficiency : a ‛two-disease’ approach |
| title_full_unstemmed |
The genetics of IgA deficiency : a ‛two-disease’ approach |
| title_sort |
genetics of iga deficiency : a ‛two-disease’ approach |
| publisher |
Inst för laboratoriemedicin / Dept of Laboratory Medicine |
| publishDate |
2015 |
| url |
http://hdl.handle.net/10616/41823 |
| genre |
Iceland |
| genre_facet |
Iceland |
| op_relation |
I. Association of immunoglobulin A deficiency and elevated thyrotropinreceptor autoantibodies in two Nordic countries. Jorgensen GH, Ornolfsson AE, Johannesson A, Gudmundsson S, Janzi M, Wang N, Hammarström L, Ludviksson BR. Hum Immunol. 2011 Feb; 72(2):166-72. ::doi::10.1016/j.humimm.2010.10.014 ::pmid::20977916 ::isi::000286644700009 II. Serologic assessment for celiac disease in IgA deficient adults. Wang N, Truedsson L, Elvin K, Andersson BA, Rönnelid J, MinchevaNilsson L, Lindqvist A, Ludvigsson JF, Hammarström L, Dahle C. [Submitted] III. Selective IgA deficiency in autoimmune diseases. Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, Rantapää-Dahlqvist S, Elvin K, Truedsson L, Andersson BA, Dahle C, Ortqvist E, Gregersen PK, Behrens TW, Hammarström L. Mol Med. 2011; 17(11-12):1383-96. ::doi::10.2119/molmed.2011.00195 ::pmid::21826374 ::isi::000297958800029 IV. High-density SNP mapping of the HLA region identifies multiple independent susceptibility loci associated with selective IgA deficiency. Ferreira RC, Pan-Hammarström Q, Graham RR, Fontán G, Lee AT, Ortmann W, Wang N, Urcelay E, Fernández-Arquero M, Núñez C, Jorgensen G, Ludviksson BR, Koskinen S, Haimila K, Padyukov L, Gregersen PK, Hammarström L, Behrens TW. PLoS Genet. 2012 Jan; 8(1):e1002476. ::doi::10.1371/journal.pgen.1002476 ::pmid::22291608 ::isi::000300223400037 V. Sequencing of the MHC region in IgA deficient individuals homozygous for HLA-A1, B8, DR3, DQ2 haplotype - a comparison with IgA sufficient blood donors. Wang N, Cao H, Zhang T, Xu Y, Wang G, Hammarström L. [Manuscript] 978-91-7549-424-1 http://hdl.handle.net/10616/41823 |
| op_rights |
info:eu-repo/semantics/openAccess |
| _version_ |
1782335922885361664 |
| spelling |
ftkarolinskainst:oai:openarchive.ki.se:10616/41823 2023-11-12T04:19:31+01:00 The genetics of IgA deficiency : a ‛two-disease’ approach Wang, Ning 2015-09-04 application/pdf http://hdl.handle.net/10616/41823 eng eng Inst för laboratoriemedicin / Dept of Laboratory Medicine I. Association of immunoglobulin A deficiency and elevated thyrotropinreceptor autoantibodies in two Nordic countries. Jorgensen GH, Ornolfsson AE, Johannesson A, Gudmundsson S, Janzi M, Wang N, Hammarström L, Ludviksson BR. Hum Immunol. 2011 Feb; 72(2):166-72. ::doi::10.1016/j.humimm.2010.10.014 ::pmid::20977916 ::isi::000286644700009 II. Serologic assessment for celiac disease in IgA deficient adults. Wang N, Truedsson L, Elvin K, Andersson BA, Rönnelid J, MinchevaNilsson L, Lindqvist A, Ludvigsson JF, Hammarström L, Dahle C. [Submitted] III. Selective IgA deficiency in autoimmune diseases. Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, Rantapää-Dahlqvist S, Elvin K, Truedsson L, Andersson BA, Dahle C, Ortqvist E, Gregersen PK, Behrens TW, Hammarström L. Mol Med. 2011; 17(11-12):1383-96. ::doi::10.2119/molmed.2011.00195 ::pmid::21826374 ::isi::000297958800029 IV. High-density SNP mapping of the HLA region identifies multiple independent susceptibility loci associated with selective IgA deficiency. Ferreira RC, Pan-Hammarström Q, Graham RR, Fontán G, Lee AT, Ortmann W, Wang N, Urcelay E, Fernández-Arquero M, Núñez C, Jorgensen G, Ludviksson BR, Koskinen S, Haimila K, Padyukov L, Gregersen PK, Hammarström L, Behrens TW. PLoS Genet. 2012 Jan; 8(1):e1002476. ::doi::10.1371/journal.pgen.1002476 ::pmid::22291608 ::isi::000300223400037 V. Sequencing of the MHC region in IgA deficient individuals homozygous for HLA-A1, B8, DR3, DQ2 haplotype - a comparison with IgA sufficient blood donors. Wang N, Cao H, Zhang T, Xu Y, Wang G, Hammarström L. [Manuscript] 978-91-7549-424-1 http://hdl.handle.net/10616/41823 info:eu-repo/semantics/openAccess info:eu-repo/semantics/doctoralThesis dok 2015 ftkarolinskainst 2023-11-01T23:37:08Z Selective IgA deficiency (IgAD) is the most common primary immunodeficiency disorder in Caucasians with a prevalence of approximately 1:600 in the general population. It is defined as serum IgA levels below or equal to 0.07 g/l with normal serum levels of IgM and IgG above the age of 4. Most IgAD individuals are asymptomatic, however, one-third suffer from respiratory and gastrointestinal infections and concomitant autoimmune diseases. IgAD is associated with several classical autoimmune disorders including Graves’ disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD) and potentially rheumatoid arthritis and myasthenia gravis (MG). As more than 95% of patients with GD are positive for thyrotropin-receptor autoantibody (TRAb), we thus investigated the prevalence of IgAD in TRAb-seropositive individuals both in Sweden and Iceland and showed that the prevalence of IgAD in the Swedish cohort is significantly higher than expected in the general population. TRAb- seropositivity is also common among IgAD individuals in both cohorts, suggesting a predisposition to GD (Paper I). There is a markedly increased prevalence of IgAD among adults with CD. It is therefore important to validate the IgG class antibody tests for screening CD in IgAD adults. IgG anti tissue transglutaminase (anti-tTG) and anti deamidated gliadin peptides (anti-DGP) antibodies were determined in our IgAD cohort with suspected CD. IgG anti-tTG seems to be a reliable marker for CD in IgAD adults whereas the diagnostic specificity of IgG anti-DGP appears to be lower. We also found that high levels of IgG antibodies against both tTG and DGP were frequently found in IgAD adults despite adhering to a gluten free diet (Paper II). We subsequently screened IgAD among patients with SLE and T1D in different ethnical populations and the observed higher prevalence of IgAD was consistent with previous publications (Paper III). IgAD is reported to be strongly associated with the MHC region, especially the HLA- A1, B8, DR3, DQ2 ... Doctoral or Postdoctoral Thesis Iceland Karolinska Institutet: Publications |