The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis

Dulic, Sonja; Vásárhelyi, Zsófia; Bajnok, Anna; Szalay, Balázs; Toldi, Gergely; Kovács, László; Balog, Attila

doi:10.1159/000484250

Cited by 29 publications

(24 citation statements)

References 24 publications

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“…Our results showed that Anbainuo injections could address partial immune function imbalance in AS patients by affecting differentiation and activation of immune cell subtypes, including naïve CD4+ T cells, Tregs, and B10 cells. Among these, the decreased proportion of naïve CD4+ T cells after Anbainuo treatment was consistent with the findings of past research [20]. Our observation that naïve We also find that Anbainuo treatment for AS can increase the proportion of negative regulatory cells such as Tregs and Bregs in inflammation that are significantly lower than normal before treatment.…”

Section: Correlation Between Immune Cells and Clinical Parameterssupporting

confidence: 92%

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TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis

Yang

Wei

et al. 2020

Preprint

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Background: Studies into ankylosing spondylitis (AS) and its relationship with immune function are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune function is unclear.Methods: A total of 40 immune cells were tested with flow cytometry, and the results of 105 HC (healthy control) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of TNF-α inhibitor therapy (Anbainuo) were analyzed.Results: Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (p<0.0001), but effector memory and terminally differentiated CD4+T cells were decreased (p<0.01 and 0.0001, respectively). Naïve, central memory, and effector memory CD8+T cells were increased (p<0.0001, 0.001, and 0.01, respectively), but terminally differentiated CD8+T cells were decreased (p<0.0001). Th1 cells (helper T cells-1), Tfh1 cells (follicular helper T cells-1), Tc1 cells (cytotoxic T cells-1), and Tregs (regulatory T cells) were lower (p<0.01, 0.05, 0.0001, and 0.001, respectively), but Th17 cells, Tfh17 cells, and Tc cells were higher (p<0.001, 0.0001 and 0.001, respectively). The proportions of total B cells and class-switched B cells were increased (p<0.05), but non-switched B cells, plasma cells, memory B cells, and immature Bregs (regulatory B cells) were lower (p<0.01, 0.0001, 0.0001, and 0.0001, respectively). After Anbainuo therapy, the percentage of naïve CD4+ T cells had decreased (p<0.05) but Tregs and B10 cells (IL-10-producing regulatory B cells) had increased (p<0.01and 0.05, respectively), and the increase in Tregs was positively correlated with the decrease in CRP (C-reactive protein) (r= 0.489, p=0.018). Conclusions: We found that active-stage AS patients have an immunity imbalance involving multiple types of immune cells, including CD4+T cells, CD8+T cells, Th cells, Tfh cells, Tc cells, Tregs, Bregs, and B cells. TNF-α inhibitor Anbainuo can not only help to inhibit disease activity but can also improve the immune imbalance of CD4+ T cells and negative regulatory cells. But CD8 + T cells have not been rescued.

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Section: Correlation Between Immune Cells and Clinical Parameterssupporting

confidence: 92%

“…An increase in Tregs during long-term anti-TNF therapy for AS has also been noted [20]. Our research further reveals a positive correlation between the reduction in CRP value and a higher frequency of Tregs.…”

Section: Correlation Between Immune Cells and Clinical Parameterssupporting

confidence: 81%

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis

Yang

Wei

et al. 2020

Preprint

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“…Despite their widespread use, the impact of TNF-blocking agents on the composition of the adaptive immune system is largely unexplored. In our two previous studies in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), in which anti-TNF therapies are also highly beneficial, we found significant differences in the T-cell subset composition among responder and non-responder patients (Dulic et al 2017(Dulic et al , 2018. Key findings were the normalization of Treg frequencies and the phenotypic pattern of a continuing T-cell activation, as reflected by several activation markers.…”

Section: Introductionmentioning

confidence: 67%

Specific T-Cell Subsets Can Predict the Efficacy of Anti-TNF Treatment in Inflammatory Bowel Diseases

Dulic

Toldi

Sava

et al. 2020

Arch. Immunol. Ther. Exp.

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The effect of TNF-blockers on T-lymphocyte subsets is largely unknown in inflammatory bowel diseases (IBDs). The aim of the present study was to analyze the prevalence of T-cell subtypes and their correlation to therapeutic response. Sixtyeight patients with Crohn's disease (CD), 46 with ulcerative colitis (UC) were enrolled. (1) The clinical course was followed after the initiation of TNF-blockers (prospective study). (2) The immunophenotype was also compared between long-term anti-TNF treated-responders and non-responders (cross-sectional study). The results were compared with those of therapynaïve patients with active disease and those in remission with non-biological immunosuppressive therapy, and with healthy controls. Fourteen subtypes of peripheral blood T cells were measured with flow cytometry. The prevalence of Th2 and Th17 cells, of HLA-DR-and CD69-positive CD4 and CD8 cells, was higher, whereas the percentage of CD45RA-positive CD4 and CD8 cells was lower in both IBDs than in controls. CD8CD69 cell frequency was lower in remission, and decreased during anti-TNF therapy in CD responders. CD8CD45RO memory cells had higher prevalence in UC non-responders than in those starting anti-TNF. CD4CD45RO percentage < 49.05 at the initiation of TNF-blockers was predictive of a subsequent therapeutic response in CD, and Th2 and Th17 prevalence correlated with the duration of remission on TNF-blockers in UC. This study provided a detailed description of the T-cell composition in IBDs. CD8CD69 prevalence may be an activity marker in CD, and CD4CD45RO, Th2 and Th17 levels could be predictive for a therapeutic response to anti-TNF.

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“…Disease-related factors and the effect of biologic drugs must be considered in the assessment of the results. The impact of biologic drugs on T cell repertoire has been reported by Dulic et al [27] . Anti-TNF drugs increases cytokines of Th2 pathways by blocking Th1 pathway [28] .…”

Section: Discussionmentioning

confidence: 85%

The Association Between Vaccine Response and sCD30 Level in Patients Using Immunomodulator Drugs and Having Received Hepatitis B Vaccination

Solay¹,

Gültuna²,

Tayşi³

2020

FLORA

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Introduction: Biologic agents like adalimumab, infliximab, etanercept, ustekunimab and golimumab used for autoimmune diseases suppress T cell-mediated immune response. The defects of cytokines related to T helper 1 and 2 cells have been detected in non-responder subjects to hepatitis B virus (HBV) vaccine. Soluble Cluster of Differentiation 30 (sCD30) is related to the balance of T helper 1/2. Therefore, we investigated the impact of sCD30 on vaccine response. To our knowledge, this is the first study to evaluate the role of sCD30 as a potential serological marker of HBV vaccine response. Materials and Methods:Seventy-five patients using biologic drugs were vaccinated with hepatitis B vaccine at a dosage of 20 or 40 µg. The serum titer of anti-HBs and sCD30 were measured four weeks after the last vaccine dose.Results: Thirty-nine (52%) of the participants were male. Mean age was 43.4 ± 11.5 years. Forty-one (54.7%) patients received standard dose HBV vaccine. Thirty-eight (50.7%) patients responded. Serum sCD30 level was similar in responders and non-responders to HBV vaccine in the whole group. However, we found an inverse relation between antibody response to HBV vaccine and sCD30 level in patients with psoriasis who received high dose vaccine regime [69.5 (28.5-131.7) pg/mL and 47.1 (32.0-80.6) pg/mL respectively, p= 0.037]. Conclusion:This study pointed out that sCD30 may play a role in hepatitis B vaccine response. Giriş: Otoimmün hastalıklarda kullanılan adalimumab, infliksimab, etanersept, ustekunimab ve golimumab gibi biyolojik ajanlar T hücre aracılı immün yanıtı baskılar. T helper 1 ve 2 ile ilişkili sitokin salınımında gelişen sorun, hepatit B virüsü (HBV) aşısına yanıtsızlıkla sonuçlanmaktadır. sCD30 T helper ½ dengesi ile ilişkilidir. Bu nedenle bu çalışmada, sCD30'un aşı yanıtı üzerindeki etkisini incelemek amaçlanmıştır. Bu çalışma bildiğimiz kadarıyla, sCD30'un HBV aşı yanıtındaki rolünü değerlendiren ilk çalışmadır. Materyal ve Metod: Biyolojik ilaç kullanan ve 20 veya 40 µg dozda hepatit B aşısı yapılan 75 hasta çalışmaya dahil edildi. Son aşıdan dört hafta sonra anti-HBs ve sCD30'un serum titresi ölçüldü. Bulgular: Hastaların 39 (%52)'u erkektir ve ortalama yaşları 43.4 ± 11.5 yıl olarak bulunmuştur. Kırk bir (%54.7) hastaya standart doz HBV aşısı yapılmıştır. Otuz sekiz (%50.7) hastanın aşı yanıtı vardı. Serum sCD30 düzeyi, HBV aşı yanıtı olan ve olmayan gruplarda benzerdi. Fakat, yüksek doz aşı yapılan psöriyazisli hastalarda HBV aşısına karşı antikor yanıtı ile sCD30 düzeyi arasında ters ilişki [sırasıyla 69.5 (28.5-131.7) pg/mL ve 47.1 (32.0-80.6) pg/mL, p= 0.037] bulunmuştur. Sonuç: Bu çalışma sCD30'un hepatit B aşı yanıtında rol oynayabileceğini işaret etmektedir.Anahtar Kelimeler: Hepatit B aşısı; sCD30; T hücre; Yanıt

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The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis

Cited by 29 publications

References 24 publications

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis

Specific T-Cell Subsets Can Predict the Efficacy of Anti-TNF Treatment in Inflammatory Bowel Diseases

The Association Between Vaccine Response and sCD30 Level in Patients Using Immunomodulator Drugs and Having Received Hepatitis B Vaccination

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