Background. Endometriosis is a comon, complex gynecological syndrom defined as the growth of endometrial glands and stroma in an extra-uterine location. It affects 5 – 20 % of women of reproductive ...age.1 Nowadays, prevailing opinion about endometriosis is based on presumption, that endometriosis is a result of changed immune system, according to autoimmune theory.2, 3 Characteristics of autoimmune disease that are also found in endometriosis are female preponderance, multiorgan involvement, family occurence, possible genetic basis, response to hormonal manipulation, tissue damage, polyclonal B lymphocite activation, immunological abnormalities in T lymphocite and B lymphocite function and associated autoimmune disease. Women with endometriosis are more frequently affected by asthma, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrom and Hashimoto’s thyroiditis. Autoimmune disease is characterized by the production of autoantibodies against components of apoptotic cells. Anti-endometrial antibodies of IgG and IgM classes could be detected in 60 % of endometriosis patients. They show reactivity in glandular epithelium and stroma. Anti-endothelial antibodies specifically react with vascular endothelium and might be with anti-endometrial antibodies partially responsible for failure of implantation leading to infertility, wich is common in endometriosis patients. Anti-nuclear antibodies are frequent serological findings in patients with autoimmune disease, and could be detected in 29–47 % of women with endometriosis.4 Generation of anti-nuclear antibodies is a risk factor for development of other autoimmune disease in women of reproductive age. Studies have shown conflicting results on the presence of anti-ovarian antibodies in the serum of endometriosis patients and in the peritoneal fluid. Their presence is one of the possible causes of infertility. Conclusions. Ethiopathogenesis of endometriosis still remains uncelar but currently available data suggest that there are many similarites between endometriosis and such autoimmune diseases as rheumathoid arthritis, systemic lupus erythematosus, Sjögren syndrom etc. Important similarity is the presence of auto-antibodies. Autoimmune theory represents a challenge and at the same time opens the possibility of a new mode of treatement of endometriosis with immunomodulators.
Background. The prevalence of premature ovarian failure (POF) of 1 % has important psychosocial consequences and impact on general health. Besides known etiology (genetic, chromosomal, infections, ...iatrogenic) autoimmunity can be the pathologic mechanism for POF. Material and methods. Eleven women with POF, with excluded other reasons for the disease except autoimmunity were included in this study. The control group consisted of 13 healthy normo-ovulatory women. In both groups targeted family and personal history was taken and determinations of: FSH, LH, TSH, prolactin, antimüllerian hormone (AMH), inhibin B, thyroid antibodies TG and TPO. At the cellular level periferal blood T-lymphocytes were analyzed by flow cytometry, on humoral level ovarian antibodies were detected with indirect immunofluorescence on human ovary sections. Quick ACTH test was performed in study group only. Results. In 9 patients POF was associated with another autoimmune disease. Six patients of the study group (55 %) presented very elevated thyroid autoantibodies TG and TPO, in the control group the levels of both autoantibodies were within normal range. Hormonal analyses in the study group exhibited the values of hypergonadotropic hypogonadism and consequently low levels of inhibin B and AMH. Lymphocyte subset in study group namely CD4+, CD19+ and CD8+ was significantly higher, while natural killer cells and regulatory T cells were significantly lower then in the control. group. In 4 patients (36 %) antiovarian autoantibodies were detected. Results of the quick ACTH test in the study group were normal. Conslusions. POF is frequently associated with autoimmune disorders. The presence of antithyroid and antiovarian antibodies together with abnormalities of the cellular immunity can potentionally represent an autoimmune mechanism of POF. The question of immunomodulatory therapy in selected patients with POF is open.
Razvija se vse več bioloških zdravil, med katerimi prevladujejo zdravila z monoklonskimi protitelesi (angl. monoclonal antibodies, mAb), ki omogočajo specifično in učinkovito zdravljenje z manj ...neželenimi učinki. Zaradi kompleksne in občutljive proteinske zgradbe mAb je treba takšna zdravila vnašati parenteralno. Intravensko apliciranje, ki prevladuje, je lahko boleče, dolgotrajno in zahteva celo hospitalizacijo. Zato je vse več zdravil z mAb v razvoju namenjenih subkutani aplikaciji, ki je hitrejša, omogoča nižje stroške zdravljenja in boljše sodelovanje bolnikov. Subkutano pa lahko vbrizgamo le majhen volumen raztopine, zato so pogosto potrebne visoke koncentracije mAb, ki lahko povečajo viskoznost raztopin in povzročijo fizikalno nestabilnost molekul mAb v njih. Zdravila z mAb zato vsebujejo pufre, stabilizatorje in pomožne snovi za znižanje viskoznosti, ki prispevajo tudi k fizikalni stabilnosti mAb. Poleg teh sestavin članek predstavi tudi pomožne snovi, ki omogočajo vbrizgati večji volumen zdravila v podkožje in kombinacije terapevtskih mAb. Opisani so tudi inovativni sistemi za subkutano apliciranje mAb, kot so kompleksi, nanoklastri, suspenzije, mikrodelci in hidrogeli, ki so še v fazi razvijanja.
Protein programirane celične smrti 1:PD-1 (Programmed cell death protein 1) je transmembranski protein, ki je izražen na celicah T, B, NK ter monocitih in dendritičnih celicah. Vezava med PD-1 in ...njegovimi ligandi zavira tumorsko celično apoptozo, spodbuja izčrpanost T-celic in preprečuje aktiven antitumorski odziv, kar posledično omogoča nemoteno rast in razvoj tumorskih celic. Zaviralca receptorja PD-1, pembrolizumab in nivolumab, že uporabljamo v zdravljenju različnih vrst napredovalega raka, kot so: melanom, nedrobnocelični karcinom pljuč, Hodgkinov limfom in karcinom ledvic. Na zdravljenje odgovori zelo različno število bolnikov, kar je odvisno od indikacije in linije zdravljenja, to je od pri 18 do 80 odstotkih bolnikov. Posebnosti zdravljenja z imunoterapijo so zelo dolgotrajne remisije, pri posameznih bolnikih pa bomo morebiti upali govoriti celo o ozdravitvi. Najpogostejši neželeni učinki so utrujenost, srbečica, izpuščaji, driska in slabost. Najresnejši neželeni učinki so imunsko pogojeni neželeni učinki in hude z infuzijo povezane reakcije. Imunsko pogojeni neželeni učinki so kolitis, tiroiditis, pneumonitis, hepatitis in nefritis.
