Autoimmuunsus ja naise viljatus II. Folliikuleid stimuleeriva hormooni vastased antikehad autoimmuunse munasarjakahjustuse markerina

Viljatutel naistel võib esineda üldine immuunsüsteemi autoimmuunne aktivatsioon, aga ka spetsiifi line munasarja koe vastu suunatud reaktiivsus. Munasarja koe vastased autoimmuunreaktsioonid on suunatud mitmete erinevate antigeenide, sh folliikuleid stimuleeriva hormooni (FSH) β-alaühiku vastu (anti-FSH). Anti-FSH antikehad reageerivad eelistatult hormooni piirkonnaga, mis määrab ära FSH kinnitumise spetsiifilisuse tema retseptorile. FSH toime on oluline nii loomulikus kui ka viljatusravi käigus stimuleeritud follikulogeneesis. Ülevaateartiklis on keskendutud viljatute naiste vereseerumis leiduvate anti-FSH antikehadega seonduvate immunoloogiliste ja kliiniliste aspektide analüüsile. Lisaks on tutvustatud anti-FSH antikehade määramise näidustusi ja võimalust Eestis. Eesti Arst 2009; 88(2):91−9

Autoimmuunsus ja naise viljatus I. Soodumus autoimmuunsete reaktsioonide tekkeks

Viljatus esineb maailmas umbes 15%-l paaridest, millest pooltel juhtudel on põhjus naisepoolne. Naise viljatuse korral esineb tihti häireid immuunsüsteemi regulatsioonis üldise autoimmuunse aktivatsiooni või spetsiifi liselt naise reproduktiivelundite vastu suunatud reaktsioonina. Ka viljatust põhjustavate günekoloogiliste haiguste või siis seni seletamatu põhjusega viljatuse korral leitakse vereseerumis sageli autoantikehi. Artiklis on antud lühiülevaade üldistest autoimmuunsetest reaktsioonidest naise viljatuses ning kirjeldatud erinevate mittespetsiifi liste autoantikehade esinemist nendel patsientidel. Eesti Arst 2009; 88(1):14−1

Review on Autoimmune Reactions in Female Infertility: Antibodies to Follicle Stimulating Hormone

Female fertility can be affected by diseases or dysfunctions of reproductive tract, neuroendocrine system, and immune system. Reproductive autoimmune failure can be associated with overall activation of immune system or with immune system reactions specifically directed against ovarian antigens. Majority of the antiovarian autoantibodies are directed against β-subunit of follicle stimulating hormone (anti-FSH). This paper summarizes a current clinical classification of female infertility in the context of general activation of autoimmunity and antiovarian autoimmunity by describing serum anti-FSH. The presence of naturally occurring anti-FSH in healthy women will be discussed. In addition, the putative impairment of ovarian folliculogenesis in case of increased production of those antibodies in infertile women will be characterized

Vereseerumi D-vitamiini sisaldus raseduse teisel kolmandikul mõjutab rasedustulemust ja ema tervist

Taust. D-vitamiin mõjutab rohkem kui 200 geeni ekspressiooni, mistõttu on see vitamiin oluline paljudes füsioloogilistes protsessides. Inimene vajab D-vitamiini kogu elu vältel, ent kriitilise tähtsusega on see raseduse ajal. Rasedad naised ja nende vastsündinud moodustavad hüpo-D-vitaminoosi riskirühma ning D-vitamiini puudulikkusest on saanud ülemaailmne probleem.Eesmärk. Analüüsida Eesti naiste rasedusaegset vereseerumi D-vitamiini sisaldust, seda määravaid tegureid ning hinnata D-vitamiini vähese sisalduse mõju ema ning lapse tervisele.Meetodid. Analüüsiti TÜ Kliinikumi naistekliiniku tervete rasedate (n = 118) anamnestilisi ning kliinilisi andmeid raseduse II trimestril ja sünnitusjärgsel perioodil ning andmeid nende vastsündinute loost. Vereseerumi D-vitamiini sisaldus määrati kemoluminestsents- immuunmeetodil. Andmete analüüsiks kasutati lineaarset ja logistilist regressioonanalüüsi ning kohandamist seoseid mõjutavatele teguritele.Tulemused. Eesti rasedate D-vitamiini sisaldus seerumis oli keskmiselt 55,0 ± 22,8 nmol/l, jäädes 79,7%-l (95% uv 71,1–86,3) uuritavatest alla referentsväärtuse (75 nmol/l) ning 17,8%-l (95% uv 11,6–26,1) esines D-vitamiini puudulikkus (≤ 30 nmol/l). D-vitamiini väärtused vereseerumis sõltusid kalendrikuust ja naise raseduseelsest kehamassiindeksist. Rasedusaegne D-vitamiini vähene sisaldus oli seotud suurema rasedusaegse kaaluiibega, vajadusega sekkuda sünnitusse, makrosoomse lapse sünniga, lapse kehvema Apgarihindega, lapse sünnijärgse kohanemisraskusega ning ema rasedusjärgse arteriaalse vererõhu kätevahelise erinevusega üle 10 mm Hg.Järeldused. D-vitamiini väike sisaldus on Eesti rasedate naiste hulgas sage ning selle peamisteks riskiteguriteks on raseduse kandmine vähese päikeseintensiivsusega kalendrikuudel ning raseduseelne rasvumine. D-vitamiini väike sisaldus mõjutab ebasoodsalt raseduse kulgu ning ema ja lapse tervisenäitajaid. Eestis suvekuudel talletatud D-vitamiini varud ei ole talviseks perioodiks piisavad. Lähtudes sellest, soovitame määrata vereseerumi D-vitamiini sisaldust hüpo-D-vitaminoosi riskirühmal ehk rasedatel naistel ning vajaduse korral seda toidulisanditena juurde manustada. Kirjanduse andmetele tuginedes näeme vajadust suurendada D-vitamiini profülaktilist doosi päevas 70–80 IU/kg

Demographic associations for autoantibodies in disease-free individuals of a European population

The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto) immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.Peer reviewe

Follicular Proinflammatory Cytokines and Chemokines as Markers of IVF Success

Cytokines are key modulators of the immune system and also contribute to regulation of the ovarian cycle. In this study, Bender MedSystems FlowCytomix technology was used to analyze follicular cytokines (proinflammatory: IL-1β, IL-6, IL-18, IFN-γ, IFN-α, TNF-α, IL-12, and IL-23;, and anti-inflammatory: G-CSF), chemokines (MIP-1α, MIP-1β, MCP-1, RANTES, and IL-8), and other biomarkers (sAPO-1/Fas, CD44(v6)) in 153 women undergoing in vitro fertilization (IVF). Cytokine origin was studied by mRNA analysis of granulosa cells. Higher follicular MIP-1α and CD44(v6) were found to correlate with polycystic ovary syndrome, IL-23, INF-γ, and TNF-α with endometriosis, higher CD44(v6) but lower IL-β and INF-α correlated with tubal factor infertility, and lower levels of IL-18 and CD44(v6) characterized unexplained infertility. IL-12 positively correlated with oocyte fertilization and embryo development, while increased IL-18, IL-8, and MIP-1β were associated with successful IVF-induced pregnancy

Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes

Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 x 10(-8)) with GDM, mapping to/near MTNR1B (P = 4.3 x 10(-54)), TCF7L2 (P = 4.0 x 10(-16)), CDKAL1 (P = 1.6 x 10(-4)), CDKN2A-CDKN2B (P = 4.1 x 10(-9)) and HKDC1 (P = 2.9 x 10(-8)). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.Peer reviewe