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Purpose. To evaluate the relationship between the expression of orbital tissue mRNA for FOXP3, CTLA-4/CD28/CD80/CD86, and CD40/CD40 and the severity of Graves’ orbitopathy (GO). Material and Methods. Orbital tissue was obtained from 26 patients with GO, with mild (n=6) or severe GO (n=20), and 7 healthy controls. The expression of mRNA of FOXP3, CTLA-4/CD28/CD80/CD86, CD40/CD40L was measured by RT-PCR. TCR and CD3 were evaluated by immunohistochemistry. Results. Higher mRNA for FoxP3 (relative expression: 1.4) and CD40 (1.27) and lower expression of CTLA-4 (0.61) were found in the GO tissues versus controls. In severe GO as compared to mild GO higher mRNA expression for FoxP3 (1.35) and CD40 (1.4) and lower expression for CTLA-4 (0.78), CD28 (0.62), and CD40L (0.56) were found. A positive correlation was found between FOXP3 mRNA and CD3 infiltration (R=0.796, P=0.0000001). Conclusions. The enhanced FOXP3 mRNA expression in GO samples may suggest the dysfunction of FOXP3 cells in the severe GO. The diminished mRNA expression of CTLA-4 in severe GO may indicate inadequate T regulatory function. The enhanced mRNA expression of CD40 in severe GO and negative correlation to CRP mRNA may suggest their role in the active and inactive GO.

Purpose. To assess FGF-β, TGF-β, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves’ orbitopathy. Patients and Methods. Orbital tissue was taken from 27 patients with GO: (1) severe GO (n=18), the mean clinical activity score (CAS) being 8.5 (SD 2.5); and (2) mild GO (n=9), the mean CAS being 2.2 (SD 0.8), and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-β, TGF-β, and COX2 in the orbital tissue was evaluated by immunohistochemical methods. Results. We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-β expression was seen in all GO. Increased FGF-β expression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO. Conclusions. Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-β and TGF-β expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO.

Abstract Background Susceptibility to Graves' disease (GD) is determined by various genetic factors; the gene encoding protein tyrosine phosphatase (PTPN22) may be one of those associated with higher risk of GD. The aim was to estimate the association of the PTPN22 gene polymorphism rs2476601:c.C>T (c.1858C>T) with the predisposition to GD within the adult north‐eastern Polish population. Methods PTPN22 gene polymorphism was analyzed in individuals with clinical GD history (n = 166) and healthy subjects (n = 154). The presence of different variants of the investigated gene polymorphism was estimated using the DNA Sanger sequencing method. Results Patients with GD had a more frequent occurrence of the T gene allele of PTPN22 gene compared to the control group, however, it was not significant (p = 0.257). Analysis of genotype distribution showed significantly more frequent occurrence of TT homozygote in GD patients compared to control individuals (p = 0.016, OR = 9.28). Patients with ophthalmopathy had a less frequent occurrence of the T gene allele of PTPN22 gene compared to patients without ophthalmopathy, however, it was not significant (p = 0.12). Occurrence of the T gene allele of PTPN22 gene in GD manifestation in those under 40‐year old was more frequent compared to individuals over 40, but the obtained difference was also not significant (p = 0.75). Conclusions Our preliminary study suggest that PTPN22:c.1858C>T gene polymorphism may be associated with a predisposition to GD within the adult north‐eastern Polish population. The studied polymorphism of the PTPN22 gene did not significantly affect the risk of ophthalmopathy developing and disease manifestation before the age of 40.

There are only few studies evaluating lymphocytes activation in the diabetic vascular complications. ICAM-1/LFA-1 adhesion molecules not only participate in the lymphocyte T proliferation but also mediate leukocyte migration to the site of inflammation. We assess a relationship between the percentage of ICAM-1 and LFA-1 expressing PBMCs and the evolution of vascular complications in T1D in children and adolescents. The study was carried out on 60 children and adolescents with T1D (aged 9-20): (a) T1D lasting 5 years (n=20), without complications c) T1D lasting >5 years complicated with microalbuminuria, arterial hypertension, diabetic retinopathy (20 n). 20 healthy volunteers, age and sex matched constituted the control group. The expression of adhesion molecules was evaluated by using three-color flow cytometry. In children and adolescents with T1D 5 years without vascular complications and in T1D with vascular disease the percentage of LFA-1+ T lymphocytes was significantly reduced in the peripheral blood (p

The purpose of the study was to evaluate the percentage of CD4+/CD8+ peripheral T cells expressing CD62L+ and CD54+ in patients with Graves' disease and to assess if these estimations could be helpful as markers of active ophthalmopathy. The study was carried out in 25 patients with Graves' disease (GD) divided into 3 groups: 1/ 8 patients with active Graves' ophthalmopathy (GO) (CAS 3-6, GO complaints pound 1 year), 2/ 9 patients with hyperthyroid GD without symptoms of ophthalmopathy (GDtox) and 3/ 8 patients with euthyroid GD with no GO symptoms (GDeu). The control group consisted of 15 healthy volunteers age and sex matched to groups 1-3. The expression of lymphocyte adhesion molecules was evaluated by using three-color flow cytometry. In GO group the percentage of CD8+CD54+, CD8+CD62L+, CD4+CD54+ and CD4+CD62L+ T cells was significantly higher as compared to controls (p

Wprowadzenie: Autoreaktywne limfocyty T są odpowiedzialne za rozwój procesu autoimmunologicznego w cukrzycy typu 1. Migracja komórek T jest inicjowana przez wzrost ekspresji L-selektyny na błonie komórkowej limfocyta. Udowodniono korelację stężenia sL-selektyny z rozwojem retinopatii cukrzycowej oraz miażdżycy i nadciśnienia tętniczego. Cel pracy: Ocena, czy ekspresja L-selektyny na limfocytach T krwi obwodowej zmienia się w przebiegu choroby poniżej 5 lat i powyżej 5 lat, oraz czy istnieje zależność między ekspresją L-selektyny na limfocytach T krwi obwodowej u dzieci a rozwojem powikłań naczyniowych w cukrzycy. Materiał i metody: Badaniami objęto 60 osób z cukrzycą typu 1 w wieku 9-20 lat, w tym 20 pacjentów z chorobą trwającą 〈5 lat, 20 pacjentów z cukrzycą 〉5 lat trwania bez powikłań naczyniowych oraz 20 pacjentów z rozpoznaną cukrzycą powyżej 5 lat z towarzyszącymi powikłaniami naczyniowymi (mikroalbuminurią, nadciśnieniem tętniczym, retinopatią). Grupę kontrolną stanowiło 20 dzieci zdrowych w wieku 6-17 lat. Ekspresję L-selektyny na błonie limfocytów T oznaczano za pomocą trójkolorowej cytometrii przepływowej (Coulter EPICS XL). HbA1c oznaczano metodą jonowymiennej chromatografii cieczowej (HPLC) na aparacie Variant (Bio-Rad). Wyniki: Odsetek limfocytów T z ekspresją L-selektyny był znamiennie podwyższony we wszystkich grupach pacjentów z cukrzycą typu 1 w stosunku do grupy kontrolnej (p

Wprowadzenie: Cukrzyca typu 1 jest chorobą, w której zasadniczą rolę odgrywają autoreaktywne limfocyty T skierowane przeciwko antygenom trzustkowym. Cząsteczki kostymulujące CD28/CTLA-4 uczestniczą w przekazywaniu sygnału koniecznego do proliferacji limfocytów T i odgrywają istotną rolę w rozwoju procesu autoimmunologicznego. Cel pracy: Ocena, czy ekspresja cząsteczek kostymulujących CD28, CTLA-4 na limfocytach T krwi obwodowej zmienia się w dynamice choroby w przypadku cukrzycy trwającej do 5 lat i dłużej niż 5 lat. Odpowiedź na pytanie, czy istnieje zależność pomiędzy ekspresją cząstek kostymulujących na limfocytach T krwi obwodowej u dzieci a rozwojem powikłań naczyniowych w cukrzycy. Materiał i metody: Badania przeprowadzono w trzech grupach pacjentów obejmujących łącznie 60 dzieci z cukrzycą typu 1 w wieku 9-20 lat: 20 pacjentów z chorobą trwającą krócej niż 5 lat, 20 pacjentów z cukrzycą powyżej 5 lat trwania bez powikłań naczyniowych, 20 pacjentów z rozpoznaną cukrzycą trwającą dłużej niż 5 lat, z towarzyszącymi powikłaniami naczyniowymi (mikroalbuminurią, nadciśnieniem tętniczym, retinopatią). Grupę kontrolną stanowiło 20 dzieci zdrowych w wieku od 6 do 17 lat. Ekspresja cząsteczek kostymulujących CD28/CTLA-4 oceniana była za pomocą trójkolorowej cytometrii przepływowej (Coulter EPICS XL). HbA1c oznaczano metodą jonowymiennej chromatografii cieczowej (HPLC) na aparacie Variant (Bio-Rad). Wyniki: Powierzchniowa ekspresja receptora CTLA-4 na limfocytach T była podwyższona w początkowej fazie cukrzycy typu 1 trwającej krócej niż 5 lat (p

The study objective was to assess chosen biochemical parameters of blood and bioelectric function of the retina in patients with T1DM. The study group consisted of 41 patients with T1DM with no signs of diabetic retinopathy. The control group included 21 pediatric patients. We performed (1) S-cone ERG testing with retina response stimulation in both eyes at the luminance of 0.1, 0.2, and 0.5 (cd × s/m2) with the 440 nm blue flash and light application of the amber background (300 ph cd/m2, 495 nm wavelength), (2) anthropometric measurements, (3) biochemical investigations: IL-17, VEGF, and ADM by the ELISA method. A comparison of the ERG results with biochemical investigations indicates a likely correlation between the worsening of retinal bioelectric function and VEGF levels growing with diabetes duration. We showed a negative correlation between ADM and HbA1c and described possible causes of ADM reduction observed in subgroup I. We demonstrated the presence of bioelectric retinal dysfunction already before the diagnosis of diabetic retinopathy, which provides new possibilities in the diagnosis of preclinical chronic complications of diabetes. The changes observed in the levels of IL-17, ADM, and VEGF suggest their involvement in the diabetic pathogenesis of eye diseases.