Gergely Toldi

Increased Prevalence of IL-17-Producing Peripheral Blood Lymphocytes in Pre-eclampsia

Citation 
Toldi G, Rigó J Jr, Stenczer B, Vásárhelyi B, Molvarec A. Increased prevalence of IL‐17‐producing peripheral blood lymphocytes in pre‐eclampsia. Am J Reprod Immunol 2011; 66: 223–229

The Frequency of Peripheral Blood CD4+ CD25high FoxP3+ and CD4+ CD25− FoxP3+ Regulatory T Cells in Normal Pregnancy and Pre‐Eclampsia

Regulatory T cells (Tregs) play an important role in the development of pregnancy‐specific immune tolerance. We aimed to determine the peripheral frequency of a recently described Treg subpopulation, the CD4+ CD25− FoxP3+ Treg subset, and its correlation with the conventional CD4+ CD25high FoxP3+ Tregs in normal pregnancy (NP) and pre‐eclampsia (PE) compared to non‐pregnant (non‐P) women. We also examined the proportion of the activated CD4+ CD25high FoxP3high Treg subset within conventional Treg cells.

Peripheral Th1/Th2/Th17/regulatory T-cell balance in asthmatic pregnancy

Asthma is a common chronic disease that may complicate pregnancy and a risk factor for complications; however, immunological mechanisms of the bilateral interactions between asthma and pregnancy are not fully understood. Healthy gestation is characterized by a sensitive balance of T(h)1/T(h)2/T(h)17/regulatory T (Treg) cells that may be altered in asthmatic pregnancy. The aim of this study was to describe the prevalence of these cell subsets in asthmatic compared with healthy pregnancy. The prevalence of T(h)1, T(h)2, T(h)17 and Treg lymphocytes was identified by cell surface and intracellular marker staining in blood samples of 24 healthy non-pregnant (HNP), 23 healthy pregnant (HP), 15 asthmatic non-pregnant (ANP) and 15 asthmatic pregnant (AP) women using flow cytometry. The T(h)1/T(h)2 cell ratio was decreased in both HP and ANP compared with HNP women; however, no further decrease was observed in the AP group. The T(h)17/Treg ratio was decreased in HP, but not in AP women, compared with HNP data. Healthy pregnancy increased Treg cell prevalence compared with HNP data (4.64% versus 2.98%; P < 0.05), and this pregnancy-induced elevation was absent in AP women (2.52% versus 4.64%; P < 0.05). T(h)17 cell prevalence was similar in the HP and HNP groups (2.78% versus 3.17%; P > 0.05). Asthma increased T(h)17 prevalence in non-pregnant patients (3.81% versus 3.17%; P < 0.05), and this asthma-specific increase of T(h)17 cell prevalence was also observed in AP patients (AP versus HP: 3.44% versus 2.78%; P < 0.05). The abnormal asthma-dependent T(h)17 elevation together with blunted Treg increase may play a role in the compromised immune tolerance characterizing asthmatic pregnancy.

The effects of Kv1.3 and IKCa1 potassium channel inhibition on calcium influx of human peripheral T lymphocytes in rheumatoid arthritis

OBJECTIVE The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx during lymphocyte activation and present a possible target for selective immunomodulation. DESIGN Case-control study. SUBJECTS AND METHODS We took peripheral blood samples from 10 healthy individuals and 9 recently diagnosed rheumatoid arthritis (RA) patients receiving no anti-rheumatic treatment. We evaluated calcium influx kinetics following activation in CD4, Th1, Th2 and CD8 cells applying a novel flow cytometry approach. We also assessed the sensitivity of the above subsets to specific inhibition of the Kv1.3 and IKCa1 potassium channels. RESULTS The peak of calcium influx in lymphocytes isolated from RA patients is reached more rapidly, indicating that they respond more quickly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. No difference was detected between Th1 and Th2 or CD4 and CD8 cells in the sensitivity to IKCa1 channel inhibition among lymphocytes of RA patients. However, specific inhibition of the Kv1.3 channel acts differentially on calcium influx kinetics in RA lymphocyte subsets. Th2 and particularly CD8 cells are inhibited more dominantly than Th1 and CD4 cells. CONCLUSION The inhibition of Kv1.3 channels does not seem to be specific enough in peripheral RA lymphocytes, since anti-inflammatory Th2 cells are also affected to a noteworthy extent.

In vivo confocal microscopic evaluation of corneal Langerhans cell density, and distribution and evaluation of dry eye in rheumatoid arthritis

Corneal Langerhans cells (LCs) offer the opportunity to gain insight into the activity of the innate immunity. We examined the density and the distribution of LCs and compared the results with dry-eye parameters in rheumatoid arthritis (RA). Fifty-two RA patients with various degrees of disease activity and 24 healthy subjects were enrolled. Peripheral and central LC number and morphology were assessed with in vivo laser confocal microscopy. In addition, ocular surface disease index (OSDI), lid parallel conjunctival folds, Schirmer test, and tear break-up time (TBUT) were evaluated. The prevalence of central and peripheral LC, and the central LC morphology values (LCM) were higher than normal in RA. Within the RA group, LC prevalence and morphology were not affected by disease activity. However, patients on anti-TNF or glucocorticosteroid (GCS) therapy exhibited normal LCM, and normal central and peripheral LC density. OSDI was higher and TBUT was lower than normal in RA. The alteration of LC in RA suggests an active inflammatory process in the cornea, which may reflect an increased activation state of the innate immune system—even in inactive stages of RA and without ocular symptoms. The results also indicate ocular effects of GCS therapy in RA.

Prevalence of Regulatory T-Cell Subtypes in Preeclampsia.

The prevalence of regulatory T cells (Tregs) is lower in preeclampsia (PE) compared with healthy pregnancy (HP). However, the proportion of recently described Treg subtypes has not been investigated.

Lymphocyte activation in type 1 diabetes mellitus: the increased significance of Kv1.3 potassium channels.

Kv1.3 and IKCa1 potassium channels participate in the maintenance of calcium-influx during lymphocyte activation. Kv1.3 channels have a prominent role in specific T cell subsets, presenting a possible target for selective immunomodulation. We investigated the impact of Kv1.3 and IKCa1 channel inhibitors on calcium-influx characteristics in human T cells in type 1 diabetes mellitus. We isolated lymphocytes from 9 healthy and 9 type 1 diabetic individuals and measured the alteration of calcium-influx with flow cytometry in the Th1, Th2, CD4 and CD8 subsets after treatment of samples with specific channel inhibitors. Our results indicate an increased reactivity of type 1 diabetes lymphocytes, which is correlated to their increased sensitivity to Kv1.3 channel inhibition. However, the contribution of Kv1.3 channels to calcium flux is not exclusive for a specific lymphocyte subset as previous reports suggest, but is characteristic for each subset investigated. Therefore, the proposed inhibition of Kv1.3 channels as a novel therapeutic approach for the treatment of type 1 diabetes mellitus may have a major effect on overall lymphocyte function in this disease.

Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis.

APCs of the ocular surface, including corneal Langerhans cells (LCs), offer the opportunity to gain insight into the activity of innate immunity. We examined corneal LCs and dry eye parameters in ankylosing spondylitis (AS). Twenty-four AS patients with varying degrees of disease activity and 24 healthy participants were enrolled. Central and peripheral LC numbers, and Langerhans cell morphology (LCM) were assessed with in vivo laser confocal microscopy. In addition, ocular surface disease index, lid parallel conjunctival folds, tear break up time, and Schirmer test were evaluated. LC densities and central LCM were greater in AS patients than in the controls. Moreover, LCM was significantly greater in patients with higher systemic inflammation according to elevated C-reactive protein (CRP). Also, tear production was greatly suppressed in patients with more severe onset of the systemic inflammation according to the Bath Ankylosing Spondylitis Disease Activity Index and elevated CRP. Greater corneal LC density and LCM in AS may reflect an increased activation state of the innate immune system of the cornea in AS, which correlates with the systemic activity of AS even without ocular symptoms. Nonetheless, higher systemic inflammation might impair tear production, and it might partly explain the dry eye mechanism.

Plasma soluble urokinase plasminogen activator receptor (suPAR) levels in systemic lupus erythematosus

Objective: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of systemic inflammation. We aimed to characterize plasma suPAR levels in SLE patients. Methods: We measured plasma suPAR, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 89 SLE patients and 29 healthy controls. Results: suPAR and ESR values were higher in SLE than in controls, while CRP levels were comparable. ROC analysis of suPAR levels indicated a cut-off value of 5.70 ng/mL to distinguish patients with high disease activity (SLEDAI >8). Conclusion: suPAR might be an objective marker for identifying SLE patients with active disease.

Hepcidin concentrations and iron homeostasis in preeclampsia.

Abstract Background: Plasma iron is increased in preeclampsia (PE) when compared to healthy pregnant women. This is in contrast to inflammation characteristic for PE. The link between iron homeostasis and inflammation is hepcidin. Our goal was to describe hepcidin concentrations and its association with iron homeostasis in PE. Methods: We obtained peripheral blood samples from 30 preeclamptic [gestational age: 36.5 (24–40) weeks] and 37 healthy pregnant women [gestational age: 36 (28–39) weeks] to determine plasma hepcidin and interleukin-6 (IL-6) concentrations, complete blood cell counts and parameters of iron homeostasis [plasma iron, transferrin and ferritin levels and total iron binding capacity (TIBC)]. Hepcidin was measured using mass spectrophotometry. The Mann-Whitney test was used for statistical analysis. Results: Plasma hepcidin, IL-6, iron and ferritin concentrations were increased (p<0.05 for all), whereas plasma transferrin, TIBC and mean corpuscular hemoglobin concentrations were lower (p<0.05 for all) in PE compared to healthy pregnant women. No differences were seen in the other parameters investigated. Conclusions: Plasma iron concentrations are increased despite high hepcidin concentrations in PE. This might indicate a resistance to the iron-decreasing action of hepcidin. Clin Chem Lab Med 2010;48:1423–6.