Characterization of DNA antigens from immune complexes deposited in the skin of patients with systemic lupus erythematosus

Background Skin lesions are common manifestations in systemic lupus erythematosus (SLE). It is still unknown what the definite pathogenesis of skin involvement was and whether DNA participated in it. Our study was designed to explore the pathogenetic role and nature of nuclear antigen (DNA) deposited in the skin lesions of patients with SLE.Methods Thirty skin samples from patients with SLE and 2 normal skin samples were studied. Extracellular DNA was evaluated by indirect immunofluorescence methods. The deposited immune complexes were extracted by cryoprecipitation, and DNA was then isolated with phenol and chloroform. DNA fragment sizes were detected by agarose gel electrophoresis. Finally, 8 different probes were used to analyze the origin of these DNA molecules using Dot hybridization.Results Extracellular DNA staining was found only in skin lesions, mainly those located in the basement membrane zone, vascular wall, and hair follicle wall. Normal skin and non-lesion SLE skin showed no fluorescence at locations outside the nuclei. There were no differences in the rate and intensity of extracellular DNA staining when comparing active phase to remission phase patients. No relationship was found between extracellular DNA and circulating anti-dsDNA antibodies. Deposited DNA fragments clustered into four bands of somewhat discrete sizes: 20 000 bp, 1300 bp, 800-900 bp, 100-200 bp. Small sized fragments (100-200 bp) were positively correlated with disease activity (P<0.05, r=0.407). Dot hybridization showed significant homology of the various extracellular DNA fragments examined with human genomic DNA, but not with DNA from the microorganisms and viruses we examined. There were also homologies between DNA samples from different individuals.Conclusions DNA and its immune complexes may contribute to the pathogenesis of skin lesions in SLE. These DNA molecules range in size from 100 bp to 20 kb and may be endogenous in origin.

Application of Conglutinin-ELISA for the detection of Circulating Immune Complexes in Sera of Patients with Epidemic Hemorrhagic Fever.

Conglutinin was extracted and purified from bovine’s sera and was used in ELISA for the detection of circulating immune complexes in the sera of patients suffering from epidemic hemorrhagic fever (EHF). The detected rates of circu-

Periodontitis and Inflammation: Plasma High Titer Naturally Occurring Anti-Glucan Antibodies Form Immune Complex with Streptococcus mutans Antigen

Atheromatous plaques usually contain antigens of the periodontitis-causing bacteria Streptococcus mutans though molecular mechanism of this incorporation remains unknown. Since vascular adhesion and inflammatory potential of Immune Complexes (IC) are known we investigated the naturally occurring plasma antibodies that recognize major antigens from S. mutans. S. mutans-binding plasma proteins (SMBP) prepared by affinity chromatography on a column of heat-killed S. mutans could recognize α- and β-linked glucose in dextran and yeast respectively but not galactose in glycoproteins. SMBP contained only three proteins, each corresponding in electrophoretic mobility to standard plasma IgG, IgA or IgM. The major positively and negatively charged protein antigens (PSMAg and NSMAg) isolated from S. mutans by electrophoresis and ion exchange chromatography respectively were recognized sugar-reversibly by the anti-β-glucan antibody (ABG) and though less avidly, by the dextran-binding immunoglobulin (DIg) in normal plasma. NSMAg addition resulted in near doubling of IC-bound immunoglobulins in immunoglobulin-rich fraction of plasma. IC isolated from above fraction after NSMAg addition had substantially more IgA and IgM content than total plasma immunoglobulins. IC formation by NSMAg was significantly inhibited by ABG- and DIg-specific sugars or by selective withdrawal of ABG or DIg from plasma. ABG and DIg being relatively high titer plasma antibodies IC formation with them suggested a possible route for vascular adhesion and damage by S. mutans and its antigens. Further, high IgA content of these ICs indicated their susceptibility to tissue uptake through cell surface galectin-1 for which IgA is the lone immunoglobulin ligand.

Is Meniere Disease Caused by a Pathological Immune Response?

The etiology of Meniere disease (MD) is unknown. Among the several factors which can provoke the disease is a pathological immune response. Objective: To investigate whether MD is due to a pathological immune reaction. Materials and methods: Immunological assay (IA) was evaluated in a consecutive study on 159 patients with MD (mean age 47.8. years) and the results compared with those from 26 patients operated on because of vestibular schwannoma (VS, mean age 54.1 years), who served as a control group. In cases of MD, transtympanic electrocochleography (ECoG) and hearing threshold were measured. Results: The average hearing level (HL) in the affected ears of patients with MD was 30 dB. Evidence of abnormal plasma protein pattern was found in 127 MD patients (80%). Elevations were found in β1-globulin (54.5%), β2-globulin (26.5%), a2-globulin (34.3%), g-globulin (17.3%), complement (CH100, 36.4%) and antinuclear antibodies (ANA, 43.4%). The onset of the disease did not correlate with the level of the plasma protein neither with the level of IgG titers. Conclusion: Elevated certain plasma proteins in patients with Meniere’s disease could be a sign that Meniere’s disease is a consequence of pathological immune reaction.

Complement Protection Against Immune Complex and Acute Glomerulonephritis

in this study serum complement mediated immune complex solubilizing capacity (CMSC) and immune complement precipitation capacity (ICPIC) of 32 children with acute glomerulonephritis (AGN) were measured. The data showed that the level of serum CMSC and ICPIC was markedly decreased in acute phase and returned to normal in the 7th week after onset of disease.Correlation analysis revealed that there were positive correlation between the level of serum CMSC and ICPIC and the serum concentration of CH50, C3, C4, but no linear correlation between the level of serum CMSC and ICPIC and the amount of CIC. These results suggest that the declined serum CMSC and ICPIC in AGN may be associ ated with the pathogenesis of AGN.

Triple hit to the kidney-dual pathological crescentic glomerulonephritis and diffuse proliferative immune complexmediated glomerulonephritis: A case report

BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.

Dynamic analysis of a sexually transmitted disease model on complex networks

In this paper,a sexually transmitted disease model is proposed on complex networks,where contacts between humans are treated as a scale-free social network.There are three groups in our model,which are dangerous male,non-dangerous male,and female.By mathematical analysis,we obtain the basic reproduction number for the existence of endemic equilibrium and study the effects of various immunization schemes about different groups.Furthermore,numerical simulations are undertaken to verify more conclusions.

Neonatal vaccination against respiratory syncytial virus infection

Respiratory syncytial virus （RSV） is the leading cause of pneumonia and bronchiolitis in infants and is the most frequent cause of lower respiratory tract infections in children. Efficacious vaccination has been a longstanding goal in neonates. Due to immaturity of the neonatal immune system, vaccination has shown limited success in stimulating the neonatal endogenous immune system. Advances in the understanding of neonatal immunology have resulted in renewed development of neonatal vaccination. In this article, we review recent advances in neonatal anti- RSV vaccination strategies, including active and passive vaccination approaches, with emphasis on the effect of maternal neutralizing antibody and the role of maternal antibody in neonatal immune modulations. Recent reports in a variety of antiviral vaccine animal models have shown that maternal antibody, different from conventional vaccination, plays an immune modulatory role in the newborn immune system. Active immunization of the pregnant mother and the offspring can effectively stimulate and maintain potent neonatal immune responses, including an endogenous cytotoxic response and neutralizing antibody generation. The induced newborn endogenous antiviral immunity can last up to 6 months, and effectively blunt viral replication. Immune complexes, formed from the integral binding of the maternal neutralizing antibody and viral vaccine antigen, may play an important role in the maternal antibody-mediated neonatal immune response. The underlying mechanisms and future perspectives are discussed.