Downi sündroom – immuunsüsteemi häiretega kromosoomihaigus

Downi sündroomi (DS) ehk 21. kromosoomi trisoomia korral esineb mitmesuguseid haigusnähte, millest osa on seotud immuunsüsteemi funktsiooni häiretega. Artiklis käsitletud uuringust ilmnes, et 15aastastel ja vanematel DS-haigetel esineb tuumavastaseid ning retikuliinivastaseid antikehi oluliselt sagedamini kui tervetel. Üksikutel haigetel leiti ka pankrease saarekeste, kilpnäärme ja mao parietaalrakkude vastaseid autoantikehi. Perifeerse vere rakkude hulgas oli DS-haigetel märkimisväärselt suurenenud mälufunktsiooni omavate CD45RO+ lümfotsüütide hulk, mis võib olla üheks autoimmuunnähtude sagedasema esinemise põhjuseks neil haigetel. Eesti Arst 2007; 86(8):506-51

Autoimmuunsus reproduktiivhäirete korral: assotsieeruvate autoantikehade ja autoantigeenide uuring

Väitekirja elektroonilisest versioonist puuduvad publikatsioonid.Infertility, biological inability of a person to contribute to conception, refers also to a couple unable to achieve pregnancy after one year of trying. Infertility touches, for a shorter or longer period, 10-15% of couples and is caused by a variety of different diseases and conditions. Autoimmunity – immune reactions targeted against self biomolecules – is shown to be involved in some certain cases of male as well as female infertility; some types of autoantibodies are in various ways related to reproductive failure. However, many corresponding autoantigens are still not identified. Furthermore, there is a kind of controversial data about the significance of the presence of certain autoantibodies in reproductive failure. This study focused on (i) characterizing common autoantibodies as a circumstantial evidence for an involvement of autoimmunity in female infertility; (ii) clarifying the situation of autoantigenic targets in female hypogonadism associated with premature ovarian failure (POF) and autoimmune polyendocrine syndrome type 1 (APS-1); (iii) finding out new testicular autoantigens besides the known ones concerning male gonadal failure and infertility. The study revealed that the non-organ-specific common autoantibodies (ANA and SMA types) are significantly more prevalent among female patients with infertility than among women of general population. Although this prevalence might be due to a variety of causes, the incidence strongly supports the argument for autoimmune reactions being involved in some cases of female infertility. Secondly, 3βHSD autoantibodies, reported as POF-associated (with 21% prevalence), appear to be seldom (prevalence 2.4%) in case of these patients. Therefore their significance as a single diagnostic biomarker for POF is modest. Thirdly, a testis-expressed protein TSGA10 reveals as an autoantigen by human testis cDNA library immunoscreening with APS-1 male patients sera. A few (7%) APS-1 male and female patients’ sera contained TSGA10 autoantibodies but without any clinical association with gonadal failure in these patients. These autoantibodies persist in an APS-1 male patient sera during 25 years follow up. However, the significance of TSGA10 autoreactivity in APS-1 remains indistinct.Infertiilsus ehk viljatus on olukord kus heteropaari üheaastase regulaarse kaitsmata seksuaalelu jooksul naine ei rasestu. Infertiilsust kogeb, lühema või pikema perioodi vältel, ligikaudu 10–15% paaridest ning põhjuste skaala on väga lai ja mitmekesine. Ühena paljudest on ka autoimmuunsus – immuunmehhanismide aktiveerumine organismi omaenese molekulaarsete struktuuride ehk autoantigeenide vastu – seotud nii mehe- kui ka naisepoolsete viljatuse põhjuste teatud tüüpidega. Mitmed vastavad autoantigeenid on aga veel identifitseerimata, samuti on viljatusega seostatud autoantikehade tähenduslikkuse koha vastuolulisi andmeid. Käesoleva uurimustöö eesmärkideks oli (i) uurida erinevate kliiniliste põhjuste tõttu tekkinud viljatusega naiste gruppides üldiste autoantikehade – kui autoimmuunsete kõrvalekallete indikaatorite – esinemist; (ii) uurida munasarjade alatalitusega seotud autoimmuunsuse sihtmärke enneaegse ovariaalse puudulikkuse (POF) ja autoimmuunse polüglandulaarse 1. tüüpi sündroomi (APS-1) korral; (iii) leida autoimmuunse patogeneesiga testiste alatalituse tekkega seotud autoantigeene, kasutades vahendina APS-1 meespatsientide seerumeid. Uurimustöö tulemused näitasid et üldiseid mitte-organspetsiifilisi autoantikehi (tüübid ANA ja SMA) esineb oluliselt sagedamini infertiilsetel naistel kui üldrahvastiku naistel. See erinevus võib olla tingitud paljudest põhjustest, kuid on siiski oluliseks kaudseks tõendiks et autoimmuunsus on seotud naiste viljatuse mõnede juhtude tekkega. Teiseks, POF patsientide vereseerumeis leitud 3βHSD autoantikehad on harvemini esinevad kui varasemad andmed näitavad (levimusmäär 2,4% versus 21%) ja on seetõttu iseseisva haigusmarkerina selle haiguse korral vähemväärtuslikud. Kolmandaks uurimustöö tulemuseks oli valk TSGA10 kui autoantigeeni identifitseerimine, inimese testise cDNA raamatukogu immunoskriinimise teel APS-1 patsientide seerumitega. TSGA10 ekspresseerub rohkelt testistes, vähemal määral ka teistes kudedes. TSGA10 autoantikehad olid seerumites sedastatavad vähestel (7%) APS-1 mees- kui ka naispatsientidel, ühel juhul koguni 25-aastase jälgimisperioodi jooksul. Ei ilmnenud aga seoseid nende autoantikehade leiu ja gonaadide puudulikkuse kliiniliste tunnuste vahel APS-1 patsientidel

Õpik kõrgkoolidele

Käesolev eestikeelne immunoloogiaõpik on tänapäevastatud versioon 2015. a ilmunud õpikust. Uue õpikuteksti kirjutamise vajaduse tingis immunoloogiateaduse ja selle meditsiiniliste rakendusvõimaluste kiire areng viimastel aastatel. Seetõttu sai autoritele oluliseks küsimuseks, mida uues versioonis kajastada ja mida mitte. Arusaadavalt on need valikud rasked, eriti kui arvestada neid mitmekesiseid teadmisi, mida on saadud uute nakkushaiguste (COVID-19 jt) immuunmehhanismide uuringutes. Kiiresti on suurenenud ka immunoregulatoorsete protsesside teaduslike andmete hulk. Tänu immuunsüsteemi kontrollpunktide mõjutamisel saadud kliiniliste uuringute tulemustele on avanenud uued võimalused kasvajate raviks. Näiteid viimase ligemale kümne aasta saavutustest immunoloogias võib tuua rohkelt ning seda kõike püüdsid autorid uues õpikuversioonis ka tasakaalustatult kajastada. Käesolevas väljaandes on mitmeid uusi jooniseid, tabeleid jm, mis peaksid lugemist hõlbustama

Increased levels of anti-BSA antibodies in children with Down syndrome

IntroductionAutoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow’s milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls.MethodsSamples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart’s Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP).ResultsOverall, levels of anti-BSA antibodies were increased in those with DS compared with controls (pConclusionIncreased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.</p

Increased levels of anti-BSA antibodies in children with Down syndrome

IntroductionAutoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow’s milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls.MethodsSamples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart’s Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP).ResultsOverall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p&amp;lt;0.0001) but this was not HLA associated.ConclusionIncreased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.</jats:sec