Pathogenesis and significance of glomerular C4d deposition in lupus nephritis: activation of classical and lectin pathways

Immune complex-mediated complement activation through the classic pathway plays a key role in the pathogenesis of lupus nephritis (LN). C4d deposition in renal tissue reflects the prognosis of systemic lupus erythematosus (SLE). The aim of the current study is to investigate the pathogenesis and clinicopathologic significance of glomerular C4d deposition in LN. We retrospectively analyzed clinical and histopathological data of 20 SLE patients with renal biopsy-proven LN and 10 non-SLE renal biopsy samples as control. LN biopsies showed varying degrees of glomerular C4d staining associated with immune complex deposits, IgG (p = 0.015), C1q (p = 0.032) and C3 (p = 0.049). 7 LN biopsies had all of C4d, C1q and C3 deposits in their glomeruli, indicative of the activation of the classical pathway, whereas 2 LN biopsies had C4d and C3 deposits without accompanying C1q deposits, indicating the activation of the lectin pathway. Glomerular C4d deposition was correlated with the LN subtype (p < 0.001). In particular, a diffusely intense and coarsely granular pattern of C4d deposition in all glomeruli was detected in class V membranous LN. However, glomerular C4d deposition was correlated with neither disease activity of SLE nor histological activity and chronicity of LN. In conclusion, the activation of the lectin pathway as well as the classical pathway seems to play a crucial role in the pathogenesis of LN. Glomerular C4d staining could be helpful for diagnosing class V membranous LN, although glomerular C4d deposition does not reflect SLE disease activity and histological activity and chronicity.     

Isolation and characterization of human and rabbit sperm tail fibrous sheath

Using mechanical and chemical dissection methods, fibrous sheath was isolated both from normal ejaculated human spermatozoa and from rabbit cauda epididymal spermatozoa. The same techniques did not produce a pure preparation of fibrous sheath from ejaculated rabbit spermatozoa, suggesting that further cross-linking and stabilization of sperm structures occurs in response to components of the seminal plasma. The isolation procedures were monitored by phase contrast microscopy and the purity of the fibrous sheath was verified by electron microscopy. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human fibrous sheath revealed at least 14 protein bands of which the most intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5 kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid composition of the purified fibrous sheath from human and rabbit spermatozoa was similar, being high in aspartic acid and/or asparagine and glutamic acid and/or glutamine, serine, alanine, leucine, lysine and glycine, but low in histidine, tyrosine and isoleucine. This composition is similar to that reported for the rat and suggests that mammalian sperm tail fibrous sheaths are composed of similar types of proteins, although there are apparent differences in protein components between species.      

DSM-IV psychiatric comorbidity according to symptoms of insomnia: a nationwide sample of Korean adults

Purpose

The diagnosis of insomnia is based on the presence of four different symptoms: difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), early morning awakening (EMA), and non-restorative sleep (NRS). This study investigated the differences in sociodemographic correlates and psychiatric comorbidity between the four symptoms of insomnia in the general population of South Korea.

Methods

A sample of the population aged 18–64 (N?=?6,510) was questioned using a face-to-face interview. Insomnia was defined as having at least one of the four following symptoms three or more times per week: DIS, DMS, EMA, and NRS. Psychiatric disorders were evaluated using the Korean version of Composite International Diagnostic Interview. Logistic regression analysis was used to test each of the sleep outcomes (DIS, DMS, EMA, or NRS) for an association with sociodemographic and clinical variables.

Results

The prevalence of DIS, DMS, EMA, and NRS were 7.9?% (95?% CI 6.6–9.5?%), 7.9?% (95?% CI 6.5–9.6?%), 4.9?% (95?% CI 3.9–6.0?%), and 14.8?% (95?% CI 12.6–17.4?%), respectively. The overall prevalence of insomnia was 19.0?% (95?% CI 16.1–22.2?%). Being separated, divorced, or widowed, being single, having a part-time job, having a psychiatric illness, and having a physical illness were all significantly related to insomnia. Older age also increased the risk of DMS and EMA, and younger age was a risk factor for NRS. The presence of most psychiatric disorders was significantly related to insomnia. However, the relationship between the psychiatric illness and each insomnia symptom varied and was dependent on the insomnia symptom.

Conclusions

Most psychiatric disorders were significantly associated with each insomnia symptom in different ways. Differences in sociodemographic and clinical correlates between the four insomnia symptoms implied the heterogeneous characteristics of insomnia as defined by the current diagnostic criteria.     

Prevalence,correlates, and comorbidities of four DSM-IV specific phobia subtypes: Results from the Korean Epidemiological Catchment Area study

Although several studies have detected differences in clinical features among specific phobias, there is a shortage of detailed national data on the on the DSM-IV SP subtypes, particularly in the Asian population. To examine the prevalence, demographic and other correlates, and co-morbidities of DSM-IV SP subtypes in a nationwide sample of Korean adults. We recruited 6510 participants aged 18–64 years for this study. Lay interviewers used the Composite International Diagnostic Interview to assess participants. We analyzed socio-demographics, health-related correlates and frequencies of comorbid mental disorders among participants with SP and each subtypes compared to unaffected adults. The prevalence of lifetime DSM-IV SP was 3.8%, and animal phobias were the most prevalent type of SP. Blood–injection–injury phobia was negatively associated with education, whereas situational phobia was positively associated with education. The strongest mental disorder comorbidity was associated with situational phobia; there is a higher probability of comorbid mood (OR=5.73, 95% CI=2.09–15.73), anxiety (OR=7.54, 95% CI=2.34–24.28), and somatoform disorders (OR=7.61, 95% CI=1.64–35.22) with this subtype. Blood–injection–injury phobia was highly associated with alcohol dependence (OR=9.02, 95% CI=3.54–23.02). Specific phobias are heterogeneous with respect to socio-demographic characteristics and comorbidity pattern. Implications of the usefulness of current subtype categories should continue to be investigated.     

Fibroblast growth factor 23 regulates renal 1,25‐dihydroxyvitamin D and phosphate metabolism via the MAP kinase signaling pathway in Hyp mice

In X‐linked hypophosphatemia (XLH) and in its murine homologue, the Hyp mouse, increased circulating concentrations of fibroblast growth factor 23 (FGF‐23) are critical to the pathogenesis of disordered metabolism of phosphate (P_i) and 1,25‐dihydroxyvitamin D [1,25(OH)₂D]. In this study, we hypothesized that in Hyp mice, FGF‐23‐mediated suppression of renal 1,25(OH)₂D production and P_i reabsorption depends on activation of mitogen‐activated protein kinase (MAPK) signaling. Wild‐type and Hyp mice were administered either vehicle or the MEK inhibitor PD0325901 (12.5 mg/kg) orally daily for 4 days. At baseline, the renal abundance of early growth response 1 (egr1) mRNA was approximately 2‐fold greater in Hyp mice than in wild‐type mice. Treatment with PD0325901 greatly suppressed egr1 mRNA abundance in both wild‐type and Hyp mice. In Hyp mice, PD0325901 induced an 8‐fold increase in renal 1α‐hydroxylase mRNA expression and a 4‐fold increase in serum 1,25(OH)₂D concentrations compared with vehicle‐treated Hyp mice. Serum P_i levels in Hyp mice increased significantly after treatment with PD0325901, and the increase was associated with increased renal Npt2a mRNA abundance and brush‐border membrane Npt2a protein expression. These findings provide evidence that in Hyp mice, MAPK signaling is constitutively activated in the kidney and support the hypothesis that the FGF‐23‐mediated suppression of renal 1,25(OH)₂D production and P_i reabsorption depends on activation of MAPK signaling via MEK/ERK1/2. These findings demonstrate the physiologic importance of MAPK signaling in the actions of FGF‐23 in regulating renal 1,25(OH)₂D and P_i metabolism. © 2011 American Society for Bone and Mineral Research     

Non‐invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological‐pathological correlation analysis

Objectives

To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis.

Methods

Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification.

Results

A total of 40 elastography scans were carried out (median creatinine 172.5 μmol/L [interquartile range 133.8–281.8 μmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8–25.7 kPa] vs 22.3 kPa [interquartile range 19.0–26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7–18.0 kPa] vs 15.6 kPa [interquartile range 14.4–18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70–0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78–0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61–0.89), 0.85 (95% CI 0.75–0.95) and 0.65 (95% CI 0.53–0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively.

Conclusions

Shear wave elastography can be used as a non‐invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.     

PLENARY LECTURES-PL1 Toxicity of perfluorooctane sulfonate and perfluorooctanoate

Persistent perfluorinated organic compounds, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are used in a variety of industrial applications. They are very stable in the environment, distribute widely in the global environment and in wild life, and are detected in human sera.