Jin-Hui Tao

IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases

IL-19, IL-20 and IL-24 are members of the IL-10 family of cytokines, the human IL-19, IL-20 and IL-24 genes are all located on the q32 region of chromosome 1, and the three cytokines also share a common receptor IL-20R1/IL-20R2 heterodimer. These cytokines due to the similarity and shared receptor usage, are quite overlapping in function. Recently, the available evidence has indicated that interaction of these cytokines with their receptors might exhibit pro-inflammatory effects on autoimmune diseases, particularly psoriasis and rheumatoid arthritis. Since an imbalance between anti- and pro-inflammatory cytokines contribute to the development of autoimune diseases, these cytokines may be implicated in the pathogenesis of autoimmunity. In this paper, we concisely discuss the biological features of IL-19, IL-20 and IL-24, and focus on their potential roles in autoimmune diseases. Hopefully the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for autoimmune diseases.

Meta-analysis of FKBP5 gene polymorphisms association with treatment response in patients with mood disorders

The aim of our study was to assess the association between FKBP5 gene polymorphisms and treatment response in patients with mood disorders using a meta-analysis. Eight separate studies that included data from 2199 subjects were identified. Meta-analysis was performed for three FKBP5 gene polymorphisms (rs1360780, rs3800373, and rs4713916). A significant association of FKBP5 gene rs4713916 polymorphism and response rate was found in patients with mood disorders (Overall: A versus G: OR=1.28, 95%CI=1.06-1.53, P=0.01; GA+AA versus GG: OR=1.32, 95%CI=1.05-1.67, P=0.02. Caucasian: A versus G: OR=1.28, 95%CI=1.06-1.55, P=0.01; GA+AA versus GG: OR=1.33, 95%CI=1.04-1.70, P=0.02). However, we did not detect the association between FKBP5 gene rs1360780 and rs3800373 polymorphisms and treatment response in patients with mood disorders (P>0.05). This meta-analysis demonstrates that treatment response in patients with mood disorders is associated with FKBP5 gene rs4713916 polymorphism, but not rs1360780 and rs3800373.

Low Level of Serum Interleukin 27 in Patients With Systemic Lupus Erythematosus

T helper 17 (TH17) cells are beginning to be implicated in the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that interleukin 27 (IL-27) controls the development of TH17. However, whether IL-27 plays a role in the development of SLE is still unclear. In the present work, we investigated the serum IL-27 level in SLE and its relations to disease activity. Fifty-six patients with SLE and 30 healthy volunteers were recruited. Serum IL-27 levels were detected by enzyme-linked immunosorbent assay. The clinical and laboratory parameters were collected from medical records or by questionnaire. The serum IL-27 level in SLE patients was significantly lower than that in healthy controls (P < 0.001). Compared with SLE patients without nephritis, patients with nephritis had a significantly decreased serum IL-27 level (P < 0.05). However, there was no significant difference between less active and more active SLE (P > 0.05). Correlation analysis between serum IL-27 levels and SLE disease activity index showed no association (P > 0.05). In summary, a decrease in serum IL-27 level in patients with SLE suggested that this cytokine might be implicated in the pathomechanism of this disease.

Prevalence and correlates of suicidal ideation in SLE inpatients: Chinese experience

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Because of double damages of body and mind, SLE patients are in a potential risk of suicide. Many factors may contribute to the occurrence of suicide in SLE: socioeconomic factors, medical factors, mental health, family support and coping style. This study aims to investigate the prevalence and correlates of suicidal ideation in SLE inpatients in China in order to determine whether they had risk of suicide, and if so, what factors should be paid more attention to prevent suicide in wards. A total of 285 SLE patients were interviewed with questionnaires on suicidal ideation and socio-demographic characteristics, Beck Depression Inventory (BDI), Family APGAR and Trait Coping Style Questionnaire (TCSQ). Disease activity was assessed with SLE Disease Activity Index. The other medical information was collected from the patients’ medical records. In total, 34.4% of SLE patients had current suicidal ideation. Significant individual risk factors for current suicidal ideation in SLE patients included having religious belief, heavy self-reported financial burdens, long duration of SLE, low level of family functioning and negative coping style. And in the presence of these risk factors, being separated, divorced or widowed, having premorbid suicidal ideation and depression were independent predictors of suicidal ideation. In summary, the rate of suicidal ideation in SLE patients in China is higher than that in other countries. Factors that contribute to risk of suicidal ideation include social and cultural domains and physical and psychological health. Although the association of suicidal ideation to religions and medical factors is still to be investigated, these findings may give some references to suicide prevention efforts for SLE patients in China.

Matrix Metalloproteinases: A Review of Their Structure and Role in Systemic Sclerosis

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

MicroRNA-29: a potential therapeutic target for systemic sclerosis.

Introduction: Systemic sclerosis (SSc) is a systemic autoimmune disease of unknown cause characterized by microvasculopathy, fibroblast activation, and excessive production of collagen, causing tissue and organ damage. Effective medical treatment for SSc is lacking because the etiology and pathogenesis of SSc are not fully understood. MicroRNAs (miRNAs) are endogenous, regulatory, single-stranded, noncoding RNAs that negatively modulate gene expression by either promoting the degradation of mRNA or down-regulating the protein production by translational repression. Among them, miRNA-29 is recently discovered as a class of miRNAs which is related to fibrotic disease. Numerous evidences have confirmed that miRNA-29 involved in the expression of extracellular matrix (ECM) and regulated organ fibrosis. These findings revealed a potential and appealing role for miRNA-29 as SSc therapeutic targets. Areas covered: This review provides a comprehensive view on the biogenesis and functions of miRNAs. We also discuss the aberrant expression of miRNA-29 in SSc, and summarize current understanding of miRNA-29 involved in the process of fibrosis. Finally, we discuss the therapeutic potential of targeting miRNA-29 in SSc. Expert opinion: Although the exact pathogenesis of SSc still remains to be clarified, Targeting miRNA-29 may serve as a promising therapy strategy.

TIM-3 as a new therapeutic target in systemic lupus erythematosus

T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) was the first surface molecule that specifically identifies Th1 cells in both mice and human. Recently, identification of Galectin-9 as a ligand for TIM-3 has established the TIM-3–Galectin-9 pathway as an important regulator of Th1 immunity and tolerance induction. Many previous studies have demonstrated that TIM-3 influences chronic autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. In addition, association of TIM-3 polymorphisms with susceptibility to several autoimmune diseases has been identified. Recent work has explored the role of TIM-3 in systemic lupus erythematosus (SLE), and their results indicate that TIM-3 may represent a novel target for the treatment of SLE. In this review, we will discuss the TIM-3 pathway and the therapeutic potential of modulating the pathway in SLE.

Interleukin-21 as a potential therapeutic target for systemic lupus erythematosus

Interleukin-21(IL-21) is the most recently discovered member of the type-I cytokine family. Structurally, IL-21 shows homology to IL-2, 4, and 15 proteins. It has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. Many previous studies have identified that IL-21 was associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. In addition, recent work has explored the role of IL-21 in systemic lupus erythematosus (SLE). Elevated expression of IL-21 was found in the sera of patients and mice with SLE. Moreover, association of IL-21 and IL-21R polymorphisms with susceptibility to SLE have been reported. All these findings suggest that IL-21 may have promise as a potential therapeutic target for SLE. In this review, we will discuss the biological features of IL-21, the IL-21 signaling and its potential role in SLE.

Association of DRD2 gene polymorphisms with mood disorders: A meta-analysis

BACKGROUND In the past few decades, a number of studies have investigated the association of dopamine D2 receptor (DRD2) gene polymorphisms with mood disorders, but the findings are not always consistent. The aim of our study was to assess the association between DRD2 gene polymorphisms and mood disorders by using a meta-analysis. METHODS Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang, with the last report up to June 2010. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2. RESULTS We identified 19 separate studies using search, but only 14 separate studies (2157 cases and 3272 controls) were included in the current study. Meta-analysis was performed for three DRD2 gene polymorphisms (-141Cins/del, Ser311/Cys311, and TaqI A1). We performed meta-analysis in overall, Caucasian, and Asian populations. We also performed disease-specific meta-analysis in unipolar disorder and bipolar disorder. We found no association between DRD2 gene -141Cins/del polymorphism and mood disorders in overall and Caucasian populations (P>0.05). We also found no association between DRD2 gene Ser311/Cys311 polymorphism and mood disorders in overall, Caucasian, and Asian populations (P>0.05). An association of DRD2 gene TaqI A1 polymorphism with mood disorders was found in overall population, and the individuals with A1A1 genotype were more susceptible to mood disorders in comparison to those with A2A1 and A2A2 genotypes (OR=1.84, 95% CI=1.07-3.17, P=0.03). LIMITATION Meta-analysis is retrospective research that is subject to the methodological deficiencies of the included studies. CONCLUSION This meta-analysis suggests that mood disorders may be associated with DRD2 gene TaqI A1 polymorphism, but not -141Cins/del and Ser311/Cys311.

Associations of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus

The objective of this study is to evaluate the association of clinical features and prognosis with age at disease onset in patients with systemic lupus erythematosus (SLE) in a large, multicenter Chinese cohort. Medical records of 1898 SLE inpatients from 15 hospitals were reviewed and classified into three groups according to their ages at disease presentation. Categorical data were analyzed by chi-square test and potentially associated factors were tested by multinomial logistic regression. Among the patients studied, 259 (13.6%) were juvenile onset (≤18 years), 1444 (76.1%) were early onset (>18 and ≤45 years) and 195 (10.3%) were late onset (>45 years). Whenever manifestations occurred, most patients (>80%) were diagnosed within two years. Juvenile-onset patients were more likely to be untreated before admission (p < 0.001) and have mucocutaneous manifestations (p < 0.001), but musculoskeletal symptoms (p < 0.05) and leukopenia (p < 0.05) were less frequent, while comorbidities were much higher in patients with late-onset SLE (p < 0.001). Neuropsychiatric, cardiopulmonary, renal and gastrointestinal involvement, disease activity index and damage scores were similar among three groups. Anti-Sm antibodies were less prevalent in late-onset patients (p < 0.05) and antimalarial drugs were more often applied to juvenile-onset patients (p < 0.001). As expected, mortality was elevated in the late-onset SLE group (p < 0.05), in which nearly half died of infections, which was much higher than those in the other two groups (p < 0.001). Logistic regression confirmed that patients with juvenile- and early-onset disease were associated with high incidence of being untreated prior to admission, and with low incidence of comorbidities as well as deaths caused by infection compared to patients with late-onset lupus. Interestingly, our data showed that more patients with late-onset disease had a SLEDAI score change of >7 at discharge. In conclusion, age at onset has an impact on SLE disease status, and infection is the main cause of death in those with late-onset lupus. Considering that the late-onset patients had simultaneously easily controllable diseases and high incidence of comorbidities, a different treatment strategy from younger patients should be considered.