Peripheral immature B cells: modulators of autoimmunity.

B cells play an essential role in humoral immunity by producing antigen-specific antibodies. However, B cells also participate in cellular immune responses by presenting antigens, providing costimulation, and producing cytokines to activate and expand effectors and memory T cell populations. Recent identification of antibody-independent functions of B cells has reawakened interest in the many roles of B cells in normal immune responses as well as in autoimmune diseases. B cells interact with other immunocompetent cells during a tightly regulated immune activation process, acting as both effector and regulator. If this balance between effector and regulatory B cell functions is disrupted, harmful effects of immune activation such as autoimmunity can occur. In this review, we will discuss the role of human peripheral immature B cells in normal immune responses as a modulator of autoimmunity. We will also discuss abnormalities of these cells in pathogenesis of systemic autoimmunity with particular focus on systemic lupus erythematosus pathogenesis.

HOXB13 regulates the prostate-derived Ets factor: implications for prostate cancer cell invasion.

HOXB13 has been shown to enhance the invasive potential of breast and endometrial tumors. HOXB13 is also abundant in castration-resistant prostate tumors. To determine the invasive potential of HOXB13 in prostate tumors, highly metastatic PC3 prostate cancer cells were manipulated to express HOXB13 and/or the prostate-derived Ets factor (PDEF). The PDEF is believed to reduce the invasive potential of various tumors, including prostate tumors. To further demonstrate the functional correlation between HOXB13 and PDEF, transwell invasion and gelatin zymography assays were performed. In addition, the western blot analysis was used to demonstrate the expression of PDEF target proteins involved in cancer cell migration and invasion, MMP-9 and survivin. According to the results, HOXB13 promoted PC3 cell migration and invasion. The DNA microarray analysis demonstrated that HOXB13 significantly suppressed the expression of the PDEF. Accordingly, the expression of MMP-9 and survivin was regulated by HOXB13. In addition, HOXB13 promoted the invasive potential of PC3 cells while inhibiting the PDEF. The coexpression of HOXB13 and the PDEF led to moderate retardation of the number of invasive cells, indicating that HOXB13 functionally counteracted cell invasion by reducing PDEF expression. The western blot analysis demonstrated that HOXB13 counteracted the PDEF-mediated inhibition of the expression of PDEF target proteins such as MMP-9 and survivin. The results suggest that the HOXB13-mediated promotion of tumor cell invasion is accomplished mainly through the downregulation of PDEF expression.

Prevalence of widespread pain and its influence on quality of life: population study in Korea.

The objective of this study was to examine the prevalence and risk factors for widespread pain and its influence on quality of life in residents of Korean communities. A rural and an urban community were selected, and 5,037 subjects were surveyed. Participants were asked if they had pain, aching, or stiffness in any of their joints on most days. Widespread pain was defined as pain above the waist, below the waist, on both sides of the body and in the axial region. The prevalence of widespread pain was 12% (16.2% and 5.5% in females and males, respectively). It was more frequent among females and increased with age in both genders. Age, female gender, and the presence of hand or knee arthritis were significantly associated with widespread pain after multivariate analysis. Except for mental health, all the items in the SF-12 were adversely affected in the widespread pain group after adjustment for confounding factors. Our findings show that the prevalence of widespread pain among residents of Korean communities is comparable to that reported among Caucasians. The significantly worse quality of life among subjects with widespread pain suggests that it may cause major health issues in the aging population.

Tibiofemoral osteoarthritis affects quality of life and function in elderly Koreans, with women more adversely affected than men.

BACKGROUND: The prevalence of knee osteoarthritis(OA) in East Asia is as common for men and even higher for women than that reported in the Caucasian population. Since both population aging and economic growth have taken place at a much faster pace in Asian countries, such as South Korea, one would expect knee OA to become a major public health problem. However, few studies have examined the influence of knee OA on the quality of life (QoL) and physical function in Asia. The aim of this cross-sectional study is to investigate the influence of knee osteoarthritis (OA) on the quality of life (QoL), function and lower extremity physical performance and the gender difference in its influence in elderly community residents in Korea. METHODS: Participants were from the population-based Hallym Aging Study (HAS). The mean age of the 504 study subjects was 70.2 years and 274 (54%) were women. Demographic information was obtained by questionnaire, and radiographic evaluations consisted of weight-bearing semi-flexed knee radiographs. Self-reported QoL and function were assessed using Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form 12-item (SF-12). Performance-based lower extremity function was assessed using the tests consisting of standing balance, usual walk and chair stands. The odds ratios(ORs) for belonging to the worst quartile of WOMAC and physical performance test were calculated by logistic regression analysis in radiographic knee OA compared to non-OA after adjustment of confounders. Scores for SF-12 items were analyzed using general linear models and means adjusted for age, BMI and OA severity were compared. RESULTS: Subjects with radiographic knee OA had significantly increased OR for belonging to the worst WOMAC quartile(for pain, 2.13,95% confidence interval[CI], 1.33-3.40, for stiffness, 2.94,95% CI,1.78-4.86, and for function, 2.97, 95% CI,1.83-4.81) and significantly worse SF-12 scores compared to non-OA after adjustment of age, BMI and sex. Women had worse WOMAC and SF-12 scores compared to men, regardless of the presence of radiographic knee OA after adjustment of age, BMI and OA severity. OA subjects had significantly worse performance score for usual walk and chair stands compared to non-OA subjects, but the ORs were no more significant after adjustment of sex. CONCLUSIONS: Knee OA negatively affects the QoL and physical function in both genders, but women are more adversely affected than men.

Clinical and radiographic features of adult-onset ankylosing spondylitis in Korean patients: comparisons between males and females.

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4+/-8.9 yr and average disease duration was 9.6+/-6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.

The prevalence of knee osteoarthritis in elderly community residents in Korea.

The purpose of this study was to estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) among community residents and to elucidate the relevant risk factors. This prospective, population-based study was conducted on residents over 50 yr of age in Chuncheon. Subjects completed an interview based on a standardized questionnaire and clinical evaluation including standardized weight bearing semiflexed knee A-P radiographs. We defined a subject with the Kellgren and Lawrence grade >or=2 as having radiographic knee OA (ROA). Symptomatic knee OA (SOA) was defined by the presence of both ROA and knee pain. We obtained symptom information and radiographs from 504 subjects. The prevalence of ROA and SOA was 37.3% and 24.2%, respectively. The prevalence of both ROA and SOA was significantly higher among women than among men. Multivariate analysis revealed that the presence of hypertension, and a manual occupation were significantly associated with the presence of ROA and SOA. Lower level of education was significantly associated with the presence of ROA, and female sex with the presence of SOA. In conclusion, both ROA and SOA are common in the aged adult population of Korea, with preponderance for women.

HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression.

During the prostate cancer (PCa) development and its progression into hormone independency, androgen receptor (AR) signals play a central role by triggering the regulation of target genes, including prostate-specific antigen. However, the regulation of these AR-mediated target genes is not fully understood. We have previously demonstrated a unique role of HOXB13 homeodomain protein as an AR repressor. Expression of HOXB13 was highly restricted to the prostate and its suppression dramatically increased hormone-activated AR transactivation, suggesting that prostate-specific HOXB13 was a highly potent transcriptional regulator. In this report, we demonstrated the action mechanism of HOXB13 as an AR repressor. HOXB13 suppressed androgen-stimulated AR activity by interacting with AR. HOXB13 did neither bind to AR responsive elements nor disturb nuclear translocation of AR in response to androgen. In PCa specimen, we also observed mutual expression pattern of HOXB13 and AR. These results suggest that HOXB13 not only serve as a DNA-bound transcription factor but play an important role as an AR-interacting repressor to modulate hormone-activated androgen receptor signals. Further extensive studies will uncover a novel mechanism for regulating AR-signaling pathway to lead to expose new role of HOXB13 as a non-DNA-binding transcriptional repressor.