Pro-inflammatory cytokines in spondyloarthritis: a case-control study.

OBJECTIVES: We aimed to determine the discriminative values of pro-inflammatory cytokines to distinguish spondyloarthritis patients from healthy subjects and to assess the association between these cytokines and spondyloarthritis characteristics. METHODS: We conducted a case-control study, including 144 subjects matched for age and sex: 72 spondyloarthritis patients(G1) and 72 controls (G2). The disease activity was assessed using ASDAS-CRP and BASDAI. Structural damage was assessed using BASRI. The levels of interleukin (IL) IL-1, IL-6, IL-8, IL-17, IL-23, and tumor necrosis factor α(TNFα) were measured. RESULTS: Each group included 57 men. The mean age was 44.84 ± 13.42 years. Except for IL-8, all cytokine levels were significantly higher in patients compared to controls (IL-1: p = 0.05, IL-6: p = 0.021, TNFα: p = 0.039, IL-17 and IL-23: p < 0.001). Cutoff values of IL-17 and IL-23 distinguishing patients in G1 from those in G2 were 17.6 and 7.96 pg/mL, respectively. TNFα level correlated to BASDAI (p = 0.029) and BASRI (p = 0.002). Multivariate analysis showed that structural damage was associated with the male gender (p = 0.017), longer disease duration (p = 0.038), and high disease activity (p = 0.044). Disease activity was associated with longer disease duration (p = 0.012) and increased IL-6 levels (p = 0.05). CONCLUSION: Our study showed that IL-17 was the ablest to distinguish between spondyloarthritis patients and controls, suggesting that IL-17 may be helpful for the diagnosis of spondyloarthritis.

Pro-inflammatory cytokines in patients with low back pain: A comparative study / Citoquinas proinflamatorias en pacientes con dolor lumbar: un estudio comparativo

Introduction and objectives: There are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain. This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls. Materials and methods: We conducted a case–control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale. Results: The mean age was 43.17±8.7 years in G1. Radicular pain was found in 37 cases with a Visual Analogic Scale of 3.03±2.5mm. The magnetic resonance imaging was performed in (G1), showing disk herniation and degenerative disk disease in 54.3% (n=25) and 45.7% of cases (n=21), respectively. The IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). IL-8 levels correlated with TNFα (0.942, p<10–3), IL-6 (0.490, p=0.011) and Visual Analogic ScaleRadicular-pain (r:0.297, p:0.047). IL-17 was higher in patients with restricted lumbar spine mobility (9.64±20.77 versus 1.19±2.54pg/mL, p:0.014). Conclusions: Our results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies.(AU)

Introducción y objetivos: Existen resultados controvertidos en cuanto al valor de la interleucina (IL) 8 y el factor de necrosis tumoral α (TNFα) séricos en pacientes con lumbalgia inespecífica. Este estudio tuvo como objetivo comparar las citoquinas proinflamatorias entre pacientes con dolor de espalda inespecífico y controles sin dolor. Materiales y métodos: Realizamos un estudio de casos y controles que incluyó a 106 participantes: 46 pacientes con dolor lumbar crónico inespecífico (G1) y 60 controles sin dolor (G0). Se midieron las IL-6, IL-8, IL-17, IL-23, IL-22 y el TNFα. Recopilamos datos demográficos y clínicos, incluidos la edad, el sexo, la duración del dolor lumbar y el dolor radicular. El grado de dolor se evaluó mediante la escala analógica visual. Resultados: La edad media fue de 43,17±8,7 años en G1. Se encontró dolor radicular en 37 casos con una escala analógica visual de 3,03±2,5mm. La resonancia magnética se realizó en G1, mostrando hernia discal y enfermedad discal degenerativa en el 54,3% (n=25) y el 45,7% de los casos (n=21), respectivamente. La IL-8 fue mayor en G1 (18,84±44,64 versus 4,34±1,23pg/ml, p=0,033). Los niveles de IL-8 se correlacionaron con TNFα (0,942, p<10−3), IL-6 (0,490, p=0,011) y escala visual analógicadolor radicular (r=0,297, p=0,047). IL-17 fue mayor en pacientes con movilidad restringida de la columna lumbar (9,64±20,77 versus 1,19±2,54pg/ml, p=0,014). Conclusiones: Nuestros resultados proporcionan evidencia de que la IL-8 y el TNFα juegan un papel en el dolor lumbar y en el dolor radicular debido a la degeneración o a hernia discal. Estos hallazgos podrían potencialmente ser utilizados por estudios futuros para desarrollar nuevas estrategias terapéuticas no específicas para el dolor lumbar.(AU)

Pro-inflammatory cytokines in patients with low back pain: A comparative study.

INTRODUCTION AND OBJECTIVES: There are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain. This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls. MATERIALS AND METHODS: We conducted a case-control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale. RESULTS: The mean age was 43.17±8.7 years in G1. Radicular pain was found in 37 cases with a Visual Analogic Scale of 3.03±2.5mm. The magnetic resonance imaging was performed in (G1), showing disk herniation and degenerative disk disease in 54.3% (n=25) and 45.7% of cases (n=21), respectively. The IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). IL-8 levels correlated with TNFα (0.942, p<10-3), IL-6 (0.490, p=0.011) and Visual Analogic ScaleRadicular-pain (r:0.297, p:0.047). IL-17 was higher in patients with restricted lumbar spine mobility (9.64±20.77 versus 1.19±2.54pg/mL, p:0.014). CONCLUSIONS: Our results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies.

Increased serum interleukin 22 levels in patients with axial spondyloarthritis.

OBJECTIVES: The role of IL-22 in radiographic axial spondyloarthritis is not fully elucidated. Thus, there is a need for new insights into this cytokine in this disease. We aimed to compare interleukin (IL)-22 level between spondyloarthritis, nonspecific-low back pain patients, and pain-free controls, and to evaluate associations between this cytokine and spondyloarthritis characteristics. METHODS: We conducted a case-control study including 62 patients with radiographic axial spondyloarthritis (G1), 46 with nonspecific low back pain (G2), and 42 healthy volunteers (G3). IL-22 was measured using Enzyme-linked immunosorbent assay. We evaluate disease activity and structural damage of spondyloarthritis. RESULTS: IL-22 level was higher in G1 than in G2 and G3 (38±40 versus14.42±8.17 versus14.3±18.67 pg/mL, p<0.01). IL-22 discriminated patients in G1 from G2 with a cutoff of 22.28pg/mL (Sensitivity: 62.9%, Specificity: 97.8%, area under the curve (AUC): 0.808). IL-22 cutoff of 19.27pg/mL discriminated patients in G1 from G3 (Sensitivity: 67%, Specificity: 94.3%, AUC: 0.855). No associations were found between IL-22 levels and disease activity and structural damage. CONCLUSIONS: Our study showed that IL-22 level was higher in radiographic axial spondyloarthritis patients compared to controls. It was also able to differentiate G1 patients from G2 and G3. This finding suggests that the IL-22 pathway showed to play a pathological role in spondyloarthritis.

Single nucleotide polymorphism of transforming growth factor-ß1 and interleukin-6 as risk factors for ovarian cancer.

INTRODUCTION: We investigated the association between common variants in TGF-ß1, IL-6 and the risk of ovarian cancer (OC) in Tunisian patients and control women. MATERIAL METHODS AND RESULTS: Study subjects comprised 71 OC cases and 74 control women. Genotyping of TGF-ß1 and IL-6 SNPs was done by real-time PCR. No differences were noted in the minor allele frequencies of the three TGF-ß1 SNPs between OC patients and controls. However, marked differences in the distribution of TGF-ß1 rs1800469 genotypes were seen between OC cases and controls (p < 0.001), with TGF-ß1 rs1800469 heterozygous (C/T) genotype being negatively associated with OC (OR [95% CI] = 0.24 [0.15-0.58]). The allelic and genotypic distributions at IL-6 polymorphisms showed a positive association between minor allele (G) at IL-6 rs1880242 variant (p = 0.0275; R [95% CI] = 1.88 [1.03-3.46]) and the occurrence of OC. In fact, the presence of T allele [G/T + T/T] decrease the risk of OC (p = 0.021; OR [95% CI] = 0.38 [0.17-0.88]). In addition, the Haploview analysis demonstrated high linkage disequilibrium (LD) between IL-6 SNPs and eight-locus haplotype analysis identified that GGAGGGGA and GGAGGGTA haplotypes are positively associated with OC risk. A negative association was shown between IL-6 haplotype (TGGGCCTA) and OC occurrence. CONCLUSIONS: Our results suggest that TGF-ß1 rs1800469, IL-6 rs1880242 variants and IL-6 haplotype (TGGGCCTA) have protective roles of OC risk. IL-6 haplotypes (GGAGGGGA and GGAGGGTA) increase OC susceptibility among Tunisian women.

Cytotoxic T lymphocyte antigen-4 gene polymorphisms and susceptibility to type 1 autoimmune hepatitis in the Tunisian population.

Genetic factors and gene polymorphisms leading to the onset of autoimmune response in autoimmune hepatitis (AIH) are still not full elucidated. Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response. We investigated 3 distinct polymorphic sites (+49A > G, CT60 G > A and -318C > T) of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology. A significant positive association with AIH susceptibility was found for the GG genotype in +49 position of the CTLA4 gene which was significantly higher in AIH patients compared to controls (28% vs 9%, p = 0.003, OR = 3.93 [1.56-9.88]). The CTLA4 A/A genotype in position CT60 was more significantly frequent in controls comparing to AIH patients and could be considered as a protective genotype for the tunisian patients. CTLA4 genotyping in position -318 did not show any statistically significant difference in genotype or allele distribution. The CTLA4 gene polymorphism in position +49 is associated to AIH susceptibility in the Tunisian population. Mutation in the CTLA4 gene may lead to a modification of the CTLA4 protein structure that could have functional relevance in AIH pathogenesis and onset.

Association of TNF-α-308 Polymorphism with Susceptibility to Autoimmune Hepatitis in Tunisians.

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology and several proinflammatory cytokines are implicated in its pathogenesis. The association of TNF-α gene polymorphism with AIH onset is not fully elucidated especially in the Tunisian population. The aim of this study was to determine the association of TNF-α (-308 G > A) polymorphism with AIH susceptibility and with TNF-α expression or clinical manifestations of AIH. A total of 50 AIH patients and 150 controls were included. Evaluation of TNF-α polymorphism was performed by ARMS PCR method. A significantly higher frequence of the AA genotype was found in AIH patients compared to controls (34 vs. 8%, p = 0.00002, OR 5.88). The frequency of the A-allele was significantly higher in patients with AIH compared to controls (55 vs. 37.3%, p = 0.002, OR 2.05). The G-allele was significantly more frequent in healthy controls compared to AIH patients [43 vs. 61.3%, p = 0.001, OR 0.47 (0.3-0.75)]. There was a positive correlation between the A/A genotype and a higher serum expression of TNF-α. The TNF*A allele confer susceptibility to AIH in the Tunisian patients and is associated with increased production of TNF-α. Anti-TNF antibodies could be an alternative to the use of corticotherapy and may avoid the exacerbated immune response in AIH.

Common variants in IL-1RN, IL-1ß and TNF-α and the risk of ovarian cancer: a case control study.

AIM OF THE STUDY: Several studies implicated altered inflammatory response in the susceptibility to ovarian cancer, and polymorphisms in inflammatory cytokines were shown to play an important role in the development of malignancies, including ovarian cancer (OC). Here we investigated the relationship between polymorphisms in IL-1ß (-511C>T), IL-1RN VNTR, TNF-α (-308G>A), and TNF RII (-322 VNTR) and OC risk in Tunisian women. METHODS AND RESULTS: Study subjects comprised 62 OC patients and 126 healthy women. Genotyping was done from genomic DNA obtained from blood simple by PCR. Positive association between IL-1RN (-VNTR) A1 allele (p = 0.0069; OR = 2.04; 95% CI:1.17-3.58) and OC risk, while negative association was seen with the A3 allele (P = 0.0034; OR = 0.09; 95% CI: 0.00-0.64), suggesting a protective role by the A3 allele. For IL-1ß (-511C>T), homozygous C/C genotype was associated with significantly increased risk of OC (p = 0.0002; OR = 4.14; 95% CI: 1.77-9.76), while heterozygote C/T genotype was linked with reduced risk of OC (p = 0.0033; OR = 0.40; 95% CI: 0.20-0.78). Furthermore, TNF-α -308A allele was significantly associated with heightened risk of OC (p = 0.016; OR = 1.70; 95% CI: 1.08-2.69), and homozygote G/G genotype was associated with decreased risk of OC (p = 0.0018; OR = 0.25; 95% CI: 0.09-0.66). In contrast, TNFRII (-322 VNTR) polymorphism was not associated with altered OC risk in the studied group. CONCLUSIONS: The significant association between IL-1RN VNTR, IL1-ß (-511), TNF-α (-308) and OC susceptibility in Tunisian women confirms a role for altered inflammatory response in ovarian cancer pathogenesis.

Genome-wide association of IL-28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C in a Tunisian population.

BACKGROUND:   A polymorphism upstream of interleukin (IL)-28B was recently identified to be associated with a 2-fold difference in sustained virologic response (SVR) to pegylated interferon-alpha and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C (CHC) virus genotype 1 (HCV-1) infection. AIM: We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. METHODS: We perform a prospective study in gastroenterology unitof tunis'military hospital in collaboration with immunology unit, military center of blood transfusion and laboratory of biochemistry of childrens' hospital of Tunis. HCV patients were genotyped as CC, CT or TT at the polymorphic site rs12979860 and TT, TG or GG at the polymorphic site rs8099917. Viral kinetics and rates of rapid virologic response (RVR, week 4) and SVR were compared by IL-28B type in a tunisian population. RESULTS: 154 patients including 80 healthy blood donors(sexratio: 1, mean age: 40.35 ±10.15 years) and 74 patients treated for CHC (39 men and 35 women; mean age = 51.7± 9.4 years) were enrolled. 35.6% of patients were genotyped as CC at the polymorphic site rs12979860 and 69.1% as TT at the polymorphic site rs8099917. The CC IL-28B type at rs12979860 was associated with a greater likelihood of SVR (77% vs 31.9%; p<0.001; OR: 7.11 [2.37-21.35]) compared with CT and TT. The CC IL-28B type at rs12979860 wasn't associated with improved of rapid virologic response (RVR). In a multivariate logistic regression model, the rs12979860 CC genotype predicted SVR (p<0.001; OR: 7.11 IC95% [2.37-21.35]). The TT IL-28B type at rs 8099917 wasn't associated with improved RVR and SVR compared with TG and GG. CONCLUSION: In treatment-naive HCV patients treated with pegylated interferon and ribavirin, a polymorphism upstream CC at the site rs12979860 of IL-28B is associated with increased sustained virologic response and effectively predicts treatment outcome.

HLA class II susceptibility to cervical cancer among Tunisian women.

The variability in host immunogenetic background, especially in human major histocompatibilty genes, has been shown to influence the susceptibility to human papillomavirus (HPV) infection and cervical neoplasia. Here, we conducted a case-control study in Tunisian women to examine the effect of genetic variation in HLA class II DRB1 and DQB1 genes on invasive cervical cancer (ICC) and squamous cell carcinoma (SCC). HLA genotyping was performed by PCR sequence-specific primers technique. The data revealed significant positive and negative associations, suggesting either predisposing or protective effects of these genes in the disease outcome. DRB1*15, alone or linked to DQB1*06, was associated with a 2.7- and 3.5-fold increase in risk for ICC, respectively. DRB1*13-DQB1*03 showed a similar 3.5 risk effect. Concerning SCC, we observed a relatively higher, about 1.2 times more, risk effect for these genetic markers. In contrast, only one haplotype - DRB1*13-DQB1*06 - provides evidence for a weak protection (about 0.3-fold reduction) of ICC and SCC. In conclusion, we suggest that HLA class II polymorphisms are involved in the genetic susceptibility to cervical cancer in Tunisian women.