A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss
IntroductionIt is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoa...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1069974/full |
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| author | Caroline Nørgaard-Pedersen Caroline Nørgaard-Pedersen Rudi Steffensen Ulrik Schiøler Kesmodel Ulrik Schiøler Kesmodel Ole Bjarne Christiansen Ole Bjarne Christiansen |
| author_facet | Caroline Nørgaard-Pedersen Caroline Nørgaard-Pedersen Rudi Steffensen Ulrik Schiøler Kesmodel Ulrik Schiøler Kesmodel Ole Bjarne Christiansen Ole Bjarne Christiansen |
| author_sort | Caroline Nørgaard-Pedersen |
| collection | DOAJ |
| description | IntroductionIt is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this association. Our group has previously found that some genetically determined immunological biomarkers are associated with RPL and the same biomarkers are also in various degrees known to predispose to autoantibody production. The aim of this study was to clarify whether the RPL-associated immunogenetic biomarkers are associated with positivity for three major classes of autoantibodies associated with RPL.MethodsIn 663 patients with RPL in whom we had results for HLA-DRB1 typing and plasma mannose-binding lectin (p-MBL) measurement, it was investigated whether there is a correlation between positivity for the autoantibodies: anticardiolipin antibodies, β2 glycoprotein I antibodies, and lupus anticoagulant (jointly called antiphospholipid antibodies), thyroid-peroxidase antibodies, and antinuclear antibodies and each of the HLA-DRB1 alleles HLA-DRB1*03 or HLA-DRB1*07 either alone or in combination with low p-MBL defined as ≤500 µg/l.ResultsAlthough slightly higher frequencies of positivity of two or more autoantibodies were seen in patients with either p-MBL ≤500 µg/l or being positive for HLA-DRB1*03, none were significantly associated. However, in patients with the combination of low p-MBL and HLA-DRB1*03, presence of at least one autoantibody was significantly more frequent than in patients with no such combination (OR= 2.4; 95% CI 1.2-5.0, p = 0.01). In an analysis of which autoantibodies were most strongly associated with the low p-MBL/HLA-DRB1*03 combination, antinuclear antibodies were significantly more frequent in these patients (OR 2.0; 95% CI 1.0-3.9, p=0.05) whereas the other autoantibodies were also positively but more weakly associated with this combination.DiscussionIn conclusion, to clarify the pathogenetic background, underlying immunogenetic factors should be examined in autoantibody positive RPL patients (as well as other patients with autoimmune diseases) but the genetic background may be complex. |
| first_indexed | 2024-04-10T20:12:44Z |
| format | Article |
| id | doaj.art-c0c80cf0e4194762a77a09932ed962b8 |
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| language | English |
| last_indexed | 2024-04-10T20:12:44Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-c0c80cf0e4194762a77a09932ed962b82023-01-26T09:01:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.10699741069974A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy lossCaroline Nørgaard-Pedersen0Caroline Nørgaard-Pedersen1Rudi Steffensen2Ulrik Schiøler Kesmodel3Ulrik Schiøler Kesmodel4Ole Bjarne Christiansen5Ole Bjarne Christiansen6Centre for Recurrent Pregnancy loss of Western Denmark, Department of Obstetrics and Gynaecology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkDepartment of Clinical Immunology, Aalborg University Hospital, Aalborg, DenmarkCentre for Recurrent Pregnancy loss of Western Denmark, Department of Obstetrics and Gynaecology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkCentre for Recurrent Pregnancy loss of Western Denmark, Department of Obstetrics and Gynaecology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkIntroductionIt is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this association. Our group has previously found that some genetically determined immunological biomarkers are associated with RPL and the same biomarkers are also in various degrees known to predispose to autoantibody production. The aim of this study was to clarify whether the RPL-associated immunogenetic biomarkers are associated with positivity for three major classes of autoantibodies associated with RPL.MethodsIn 663 patients with RPL in whom we had results for HLA-DRB1 typing and plasma mannose-binding lectin (p-MBL) measurement, it was investigated whether there is a correlation between positivity for the autoantibodies: anticardiolipin antibodies, β2 glycoprotein I antibodies, and lupus anticoagulant (jointly called antiphospholipid antibodies), thyroid-peroxidase antibodies, and antinuclear antibodies and each of the HLA-DRB1 alleles HLA-DRB1*03 or HLA-DRB1*07 either alone or in combination with low p-MBL defined as ≤500 µg/l.ResultsAlthough slightly higher frequencies of positivity of two or more autoantibodies were seen in patients with either p-MBL ≤500 µg/l or being positive for HLA-DRB1*03, none were significantly associated. However, in patients with the combination of low p-MBL and HLA-DRB1*03, presence of at least one autoantibody was significantly more frequent than in patients with no such combination (OR= 2.4; 95% CI 1.2-5.0, p = 0.01). In an analysis of which autoantibodies were most strongly associated with the low p-MBL/HLA-DRB1*03 combination, antinuclear antibodies were significantly more frequent in these patients (OR 2.0; 95% CI 1.0-3.9, p=0.05) whereas the other autoantibodies were also positively but more weakly associated with this combination.DiscussionIn conclusion, to clarify the pathogenetic background, underlying immunogenetic factors should be examined in autoantibody positive RPL patients (as well as other patients with autoimmune diseases) but the genetic background may be complex.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1069974/fullHLA class IImannose-binding lectinautoantibodiesantiphospholipid antibodiesrecurrent pregnancy losshabitual abortion |
| spellingShingle | Caroline Nørgaard-Pedersen Caroline Nørgaard-Pedersen Rudi Steffensen Ulrik Schiøler Kesmodel Ulrik Schiøler Kesmodel Ole Bjarne Christiansen Ole Bjarne Christiansen A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss Frontiers in Immunology HLA class II mannose-binding lectin autoantibodies antiphospholipid antibodies recurrent pregnancy loss habitual abortion |
| title | A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss |
| title_full | A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss |
| title_fullStr | A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss |
| title_full_unstemmed | A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss |
| title_short | A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss |
| title_sort | combination of the hla drb1 03 phenotype and low plasma mannose binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss |
| topic | HLA class II mannose-binding lectin autoantibodies antiphospholipid antibodies recurrent pregnancy loss habitual abortion |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1069974/full |
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