<b>BACKGROUNDb>SmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119antibody in the diagnosis of cSLE.

<b>METHODSb>Samples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P< 0.05 was considered statistically significant.

<b>RESULTSb>Thirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26.1%, χ2 = 25.1, P< 0.05) and a lower specificity (90.8% vs. 100%, χ2 = 13.6, P< 0.05) in the diagnosis of cSLE. Further analysis revealed that anti-SmD183-119antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119 was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria.

<b>CONCLUSIONSb>Measurement of anti-SmD183-119in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sm. It has been suggested that inclusion of anti-SmD183-119testing in the integrated laboratory diagnosis of cSLE may significantly improve the overall sensitivity in child populations.

Autoantibodies ; immunology ; Autoantigens ; immunology ; Child ; Female ; Humans ; Immune System Diseases ; immunology ; Immunoblotting ; Lupus Erythematosus, Systemic ; immunology ; Male ; Peptides ; chemistry ; immunology ; snRNP Core Proteins ; immunology

<b>OBJECTIVEb>To investigate the relationship between the levels of antidesmoglein (DSG) 1, 3 antibodies in the sera of patients with paraneoplastic pemphigus (PNP) and alopecia.

<b>METHODSb>Sera from PNP patients, bullous pemphigoid patients, and normal healthy subjects were collected and 2 tissue samples from 2 healthy scalps were resected. Anti-DSG 1, 3 antibodies in the sera of PNP patients were detected by enzyme-linked immunosorbent assay (ELISA). Indirect immunofluorescent assay was used to detect whether the antibodies in the sera of PNP patients binds with the follicular epithelium of normal healthy scalp.

<b>RESULTSb>Anti-DSG3 autoantibody was strongly positive and anti-DSG1 weakly positive in one patient, while both two antibodies were negative in the other patient. Their sera could bind to keratinocytes and follicular epithelium in human scalp. Immunofluorescent signals were found on the intercellular epidermal cell surface and outer root sheath of the follicular epithelium. However, the immunofluorescent signals in the section incubating with serum of bullous pemphigoid were only found on basal membrane zone. No signals were found in the section incubating with normal healthy serum.

<b>CONCLUSIONb>Alopecia in PNP patients are correlated with the anti-DSG3.

Adult ; Alopecia ; etiology ; immunology ; Autoantibodies ; blood ; Desmoglein 1 ; immunology ; Desmoglein 3 ; immunology ; Female ; Humans ; Male ; Paraneoplastic Syndromes ; complications ; immunology ; Pemphigus ; complications ; immunology

The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as ‘find-me' and ‘eat-me' signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment.
Apoptosis ; Autoantigens ; Homeostasis ; Phagocytes ; Signal Transduction

<b>OBJECTIVEb>Prader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome. The purpose of this study was to show the molecular genetic defects and genomic imprinting basis in Chinese PWS patients and to evaluate the clinical applications of a differential diagnostic test for PWS.

<b>METHODSb>Fluorescence in situ hybridization (FISH) and methylation-specific PCR (MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using three probes, including SNRPN probe for identification of the critical locus in PWS region, D15Z1 and PML control probes for identification of the 15p arm and 15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on sodium bisulfite treatment of DNA and PCR primers specific for the maternal and paternal allele.

<b>RESULTSb>When hybridized with mixed probes, it was found in 2 patients that the central specific signal was absent, but both the flanking control signals were retained, indicating SNRPN gene deletion of chromosome 15q11-13. Bisulfite-modified DNA from all PWS children amplified with methylated allele-specific primer pair showed only maternal 131bp PCR product, indicating the maternal uniparental disomy (UPD15).

<b>CONCLUSIONb>Genomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other cyto-molecular tests and its results were consistent with the clinical diagnosis of PWS, so it seems to be a reliable diagnostic method for PWS patients who show abnormal methylation at SNRPN. The genetic differential tests for PWS are important in determining familial recurrence risk.

Adolescent ; Autoantigens ; Chromosome Deletion ; Chromosomes, Human, Pair 15 ; genetics ; Gene Deletion ; Genomic Imprinting ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymerase Chain Reaction ; methods ; Prader-Willi Syndrome ; genetics ; Ribonucleoproteins, Small Nuclear ; genetics ; snRNP Core Proteins

BACKGROUND: Desmogleins are transmembrane glycoproteins of the desmosome which provide mechanical strength to epithelial tissue. Desmogleins have so far, been implicated in several diseases such as pemphigus, striate palmoplantar keratoderma, 4S and squamous cell carcinomas. Skin cancer usually occurs in old age. And there are reports that the expression of desmogleins are increased in squamous cell carcinoma. However the role of desmogleins in skin aging has not yet been reported. OBJECTIVE: The purpose of this study was to investigate the expression of desmoglein 1 and 3 according to chronologic skin aging. METHODS: A total of 6 normal tissue samples from sun-protected skin of different age groups (from 34-year-old to an 84-year-old) and 1 squamous cell carcinoma tissue from a 72-year-old patient were taken. Western blotting and immunohistochemical staining were performed with anti desmoglein 1 and 3 antibodies. The expression of desmoglein 1 and 3 by Western blotting were calculated semiquantitatively by a densitometer. RESULTS: The expression of desmoglein 1 was 0.382 in the 34-year-old, 0.450 in the 45-year-old, 0.369 in the 56-year-old, 0.761 in the 65-year-old, 1.035 in the 77-year-old and 1.329 ODu/mm2 in the 84-year-old. The expression of desmoglein 3 was 0.830 in the 34-year-old, 0.984 in the 45-year-old, 1.029 in the 56-year-old, 1.534 in the 65-year-old, 1.714 in the 77-year-old and 1.878 ODu/mm2 in the 84-year-old. In immunohistochemical staining, the expression of Dsg1 increased from the basal layer to the granular layer and Dsg3 was expressed in the basal and suprabasal layers. CONCLUSION: The expression of desmoglein 1 and 3 were increased according to chronologic skin aging.
Adult ; Aged ; Aged, 80 and over ; Antibodies ; Blotting, Western ; Carcinoma, Squamous Cell ; Desmoglein 1* ; Desmoglein 3 ; Desmogleins* ; Desmosomes ; Glycoproteins ; Humans ; Keratoderma, Palmoplantar ; Middle Aged ; Pemphigus ; Skin Aging* ; Skin Neoplasms ; Skin*

BACKGROUND: Matrix metalloproteinases (MMPs) participate in extracellular matrix degradation and may play an important role in basal membrane damage in many dermatologic diseases. Recent studies implicated the importance of MMP-9 in the pathogenesis of bulla formation of bullous pemphigoid (BP). Various autoimmune bullous diseases are strongly associated with desmosome or hemidesmosome pathologies, and show an increased level of lesional MMP and exposed autoantigens from these structures. OBJECTIVE: This study evaluated the level of MMP-2, -3, and -9 in three types of autoimmune bullous disease [BP, pemphigus vulgaris (PV), pemphigus foliaceus (PF)] with the aim of investigating the role of MMPs in the pathogenesis of autoimmune bullous diseases. METHODS: Sample specimens were obtained from skin lesions of patients with BP (n=12), PV (n=10), and PF (n=12), and from normal controls (n=8). The immunohistochemical expression of MMP-2, -3, and -9 was analyzed and serum levels of MMP-2, -3, and -9 were measured by enzyme-linked immunosorbant assay (ELISA). The results were analyzed with reference to graded levels of clinical severity. RESULTS: Expression of dermal MMP-2, -3, and -9 were increased in BP, PV, and PF (p=0.036, 0.022, and 0.015, respectively). However, decreased expression of the three MMPs in the epidermis of skin lesions may have resulted from epidermal destruction. ELISA-determined serum levels of MMP-2, -3, and -9 increased in BP, PV and PF. Interestingly, MMP-2 was significantly increased in the sera of BP patients (p=0.015), consistent with the previous studies concerning the role of gelatinase (MMP-2 and -9) in the pathogenesis of BP. In BP patients, clinical severity was proportional to increased levels of MMP-2 in both skin lesions and and sera. CONCLUSION: The increased expression of MMP-2, -3, and -9 in skin lesions and sera may reflect the involvement of these enzymes in the mechanism of bulla formation in autoimmune bullous diseases including BP. In addition, expression of MMP and clinical severity may be closely connected.
Autoantigens ; Blister ; Desmosomes ; Epidermis ; Extracellular Matrix ; Gelatinases ; Hemidesmosomes ; Humans ; Matrix Metalloproteinases ; Membranes ; Pemphigoid, Bullous ; Pemphigus ; Skin

Frontal fibrosing alopecia (FFA) is a rare subtype of cicatricial alopecia. It was first described in 1994 by Kossard as postmenopausal frontal fibrosing alopecia. Patients who suffer from FFA show typical frontal hairline recession, and most patients experience eyebrow loss. It usually affects mainly post-menopausal women but the hormonal change due to menopause is unclear. Etiology of FFA is not clear, but it is assumed that certain autoantigens in the frontal and eyebrow hair follicles play a key role in its pathogenesis. There is no optimal treatment thus far. However, recently, topical calcineurin inhibitor was shown to be effective in early stage FFA via follicular targeted T-cell inhibition. Here, we report a case of a premenopausal 50-year-old female patient suffering from FFA displaying typical clinical features and minimal fibrosis around follicles by histological examination, which were improved by treatment with short-term systemic steroid and long-term topical calcineurin inhibitor.
Alopecia ; Autoantigens ; Calcineurin ; Eyebrows ; Female ; Fibrosis ; Hair Follicle ; Humans ; Menopause ; Middle Aged ; Stress, Psychological ; T-Lymphocytes

Neutrophils are the major antimicrobial cells of the innate immune system, which are recruited rapidly to the sites of infection and provide the primary defense against pathogens. Recent evidence suggests that neutrophils undergo a distinct cell death mechanism called NETosis, which not only contributes to the host defense, but also leads to severe pathological immune responses in cases of dysregulation. Here, we review the general features of NETosis as well as the generation of autoantigens and damage-associated molecular patterns by NETosis in autoimmune diseases. This review discusses the pathogenic role of NETosis in rheumatoid arthritis and systemic lupus erythematosus, where neutrophils may play a key role in the pathogenesis of these diseases, and suggest the possibility of neutrophil extracellular traps as biomarkers and therapeutic targets for the treatment of autoimmune diseases.
Arthritis, Rheumatoid ; Autoantigens ; Autoimmune Diseases* ; Biomarkers ; Cell Death ; Immune System ; Lupus Erythematosus, Systemic ; Neutrophils

Production of high affinity antibodies for antigens is a critical component for the immune system to fight off infectious pathogens. However, it could be detrimental to our body when the antigens that B cells recognize are of self-origin. Follicular helper T, or Tfh, cells are required for the generation of germinal center reactions, where high affinity antibody-producing B cells and memory B cells predominantly develop. As such, Tfh cells are considered as targets to prevent B cells from producing high affinity antibodies against self-antigens, when high affinity autoantibodies are responsible for immunopathologies in autoimmune disorders. This review article provides an overview of current understanding of Tfh cells and discusses it in the context of animal models of autoimmune diseases and allograft rejections for generation of novel therapeutic interventions.
Allografts* ; Antibodies ; Autoantibodies ; Autoantigens ; Autoimmune Diseases* ; Autoimmunity ; B-Lymphocytes ; Germinal Center ; Immune System ; Memory ; Models, Animal

<b>BACKGROUNDb>Patients with systemic lupus erythematosus often have various autoantibodies. The relationship between these antibodies is still poorly understood. The aim of the present study was to observe the anti-SSB antibody and anti-dsDNA antibody production profiles following immunization with synthetic SSB peptide alone, DNA alone or co-immunization with these two antigens.

<b>METHODSb>SSB 214 - 225 aa peptide was synthesized by organic chemistry solid-phase peptide synthesis. Rabbits were immunized with the following antigens: synthetic SSB peptide linked with keyhole limpet hemocyanin (KLH), DNA, SSB plus dsDNA, KLH and PBS. Antibodies were measured by ELISA. Histopathology and direct immufluorescence assays were also applied.

<b>RESULTSb>Anti-SSB and anti-dsDNA antibodies were produced following immunization with SSB peptide and DNA respectively. The level of SSB antibody in the co-immunization group was higher than that of the SSB peptide immunization group. The level of anti-dsDNA antibody in the co-immunization group was, however, lower than that in the DNA immunization group. Meanwhile, the level of anti-SSB antibody was higher than that of anti-DNA antibody in the co-immunization group. No morphological or immunological abnormalities were found in the heart, liver, kidney, spleen or skin tissues.

<b>CONCLUSIONb>Inhibition of anti-dsDNA-antibody was induced by co-immunization with synthesized SSB peptide and DNA, which might explain, at least partly, the mild disease in some LE subsets associated with SSB antibody.

Animals ; Antibodies, Antinuclear ; biosynthesis ; Autoantigens ; immunology ; DNA ; immunology ; Fluorescent Antibody Technique, Direct ; Immunization ; Rabbits ; Ribonucleoproteins ; immunology