RESUMO
The main expression sites of HLA-G are human extravillous trophoblast cells. The interaction of HLA-G with uterine NK cells promotes their maturation and differentiation into decidual NK (dNK) cells. dNK cells secrete chemokines, cytokines, and proangiogenic factors in favor of a vascular remodeling and an immune suppressive microenvironment of the decidua. HLA-G is the most polymorphic member of the oligomorphic non-classical HLA molecule family; yet, the impact of polymorphic differences is not comprehensively understood. sHLA-G levels in embryo culture medium correlate with successful pregnancy; however, it remains questionable if HLA-G allelic diversity impacts on the outcome of dNK cell development. We utilized synthetic sHLA-G*01:01, 01:03, and 01:04 molecules and transduced K652/mHLA-G*01:01, 01:03, and 01:04 cells to study the biological interaction between HLA-G alleles and primary NK cells of human term placenta. Despite its low frequency, HLA-G*01:04 and not the most prevalent allele HLA-G*01:01 appear to be strong catalysts of dNK cell proliferation. Concluding, this study illustrates novel insights into the impact and binding efficiency of the three most common variants of HLA-G on primary placental NK cells.
Assuntos
Antígenos HLA-G/genética , Células Matadoras Naturais/metabolismo , Placenta/citologia , Antígeno CD56/metabolismo , Proliferação de Células , Decídua/citologia , Feminino , Antígenos HLA-G/imunologia , Antígenos HLA-G/metabolismo , Humanos , Células K562 , Células Matadoras Naturais/imunologia , GravidezRESUMO
BACKGROUND: Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases. OBJECTIVE: There are conflicting data from studies as to an impact on allergic sensitization and asthma. METHODS: Our prospective double-blind study randomly assigned 131 children (6-24 months old) with at least two wheezing episodes and a first-degree family history of atopic disease to 6 months of Lactobacillus rhamnosus (LGG, 10(10) colony forming units) or placebo. Atopic dermatitis and asthma-related events (e.g. need of inhalation, symptom-free days) were documented throughout the intervention and 6-month follow-up. We determined IgE, a representative panel of specific IgE, eosinophils, eosinophilic cationic protein, and TGF-beta before, at the end of intervention, and after 6 months of follow-up. RESULTS: There were no significant differences as to atopic dermatitis or asthma-related events. In a subgroup with antecedent allergic sensitizations, asthmatic complaints were even slightly worse. We found fewer sensitizations towards aeroallergens after 6 months of LGG (P=0.027) and after 6 months of follow-up (P=0.03). Supplementation was well-tolerated and no severe adverse events occurred. CONCLUSIONS: In young children with recurrent wheeze and an atopic family history, oral LGG had no clinical effect on atopic dermatitis or asthma-related events, and only mild effects on allergic sensitization. This effect persisted 6 months after the cessation of the supplementation.