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Autoantibody Profile (autoantibody + profile)
Selected AbstractsEsophageal manometry in 28 systemic sclerosis Brazilian patients: findings and correlationsDISEASES OF THE ESOPHAGUS, Issue 8 2009D. C. Calderaro SUMMARY Systemic sclerosis (SSc) is a multisystem disease of unknown etiology. Esophageal involvement affects 50,90% of patients and is characterized by abnormal motility and hypotonic lower esophageal sphincter. Data on the association of esophageal abnormalities and age, gender, SSc subset or duration, autoantibody profile, esophageal symptoms, and medication are lacking or conflicting. The aim of this study was the evaluation of these associations in Brazilian sclerodermic patients from the Rheumatology Division, Clinics Hospital, Federal University, Minas Gerais. They underwent medical records review, clinical interview, and esophageal manometry. The normal cutoff level for lower esophageal sphincter pressure was 14 mmHg. Abnormal peristalsis occurred when less than 80% of peristaltic waves were propagated. P -values less than 0.05 were considered significant. Twenty-eight patients were included: 71% were women. The population presented medium age and disease duration of 46 years and 12 years, respectively. Cutaneous diffuse SSc occurred in 39% and its limited form in 61%. Dysphagia, pyrosis, and regurgitation occurred, respectively, in 71%, 43%, and 61% of patients. Lower esophageal sphincter pressure and number of peristaltic waves-propagated medias were, respectively, 17.2 mmHg and 2.3. SSc-related manometric abnormalities were present in 86% of patients. Manometry revealed distal esophageal body hypomotility, hypotonic lower esophageal sphincter, or both, respectively, in 82%, 39%, and 36% of patients. One patient presented the manometric pattern of esophageal achalasia. Male patients more frequently presented hypotonic inferior esophageal sphincter. Manometric findings have had no relationship with the other variables. Nifedipine use did not influence manometric findings. [source] Association of the FAM167A,BLK region with systemic sclerosisARTHRITIS & RHEUMATISM, Issue 3 2010Ikue Ito Objective An association of single-nucleotide polymorphisms (SNPs) in the FAM167A (previously referred to as C8orf13),BLK region with systemic lupus erythematosus (SLE) has been demonstrated in Caucasians and in Asians. Recent studies have shown that many genes, including IRF5, STAT4, and PTPN22, are shared susceptibility genes in multiple autoimmune diseases. We undertook the current study to examine whether the FAM167A,BLK region is also associated with susceptibility to systemic sclerosis (SSc). Methods Japanese patients with SSc (n = 309) and healthy controls (n = 769) were enrolled in a 2-tiered case,control association study. In tier 1, 124 patients and 412 controls were tested to determine association of 16 tag SNPs encompassing the FAM167A,BLK region with SSc. In tier 2, an additional 185 patients and 357 controls were analyzed for SNP rs13277113. Results Two haplotype blocks that correspond approximately to FAM167A and BLK were observed. In tier 1 of the study, the rs13277113A allele in the BLK block exhibited the most significant association with SSc after correction for multiple testing (permutated P = 0.024). Two SNP haplotypes formed by rs13277113 and the most significant SNP in the FAM167A block did not exhibit stronger association. When samples from tier 1 and tier 2 were combined, the rs13277113A allele was significantly associated with SSc (odds ratio 1.45 [95% confidence interval 1.17,1.79], P = 6.1 × 10,4). Association or a tendency toward association of rs13277113A with SSc was observed regardless of a patient's autoantibody profile or whether a patient had diffuse cutaneous or limited cutaneous SSc. Conclusion Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A,BLK region is a common genetic risk factor for both SLE and SSc. [source] Genetic variation at the IRF7/PHRF1 locus is associated with autoantibody profile and serum interferon-, activity in lupus patientsARTHRITIS & RHEUMATISM, Issue 2 2010Rafah Salloum Objective Interferon-, (IFN,) is a heritable risk factor for systemic lupus erythematosus (SLE). Genetic variation near IRF7 is implicated in SLE susceptibility. SLE-associated autoantibodies can stimulate IFN, production through the Toll-like receptor/IRF7 pathway. This study was undertaken to determine whether variants of IRF7 act as risk factors for SLE by increasing IFN, production and whether autoantibodies are important to this phenomenon. Methods We studied 492 patients with SLE (236 African American, 162 European American, and 94 Hispanic American subjects). Serum levels of IFN, were measured using a reporter cell assay, and single-nucleotide polymorphisms (SNPs) in the IRF7/PHRF1 locus were genotyped. Results In a joint analysis of European American and Hispanic American subjects, the rs702966 C allele was associated with the presence of anti,double-stranded DNA (anti-dsDNA) antibodies (odds ratio [OR] 1.83, P = 0.0069). The rs702966 CC genotype was only associated with higher serum levels of IFN, in European American and Hispanic American patients with anti-dsDNA antibodies (joint analysis P = 4.1 × 10,5 in anti-dsDNA,positive patients and P = 0.99 in anti-dsDNA,negative patients). In African American subjects, anti-Sm antibodies were associated with the rs4963128 SNP near IRF7 (OR 1.95, P = 0.0017). The rs4963128 CT and TT genotypes were associated with higher serum levels of IFN, only in African American patients with anti-Sm antibodies (P = 0.0012). In African American patients lacking anti-Sm antibodies, an effect of anti-dsDNA,rs702966 C allele interaction on serum levels of IFN, was observed, similar to the other patient groups (overall joint analysis P = 1.0 × 10,6). In European American and Hispanic American patients, the IRF5 SLE risk haplotype showed an additive effect with the rs702966 C allele on IFN, level in anti-dsDNA,positive patients. Conclusion Our findings indicate that IRF7/PHRF1 variants in combination with SLE-associated autoantibodies result in higher serum levels of IFN,, providing a biologic relevance for this locus at the protein level in human SLE in vivo. [source] Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severityBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006N. Oyama Summary Background, Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. Objectives, To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. Methods, Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). Results, Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), ,4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) ,4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to ,4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. Conclusions, Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP. [source] Development of a novel ELISA system for detection of anti-BP180 IgG and characterization of autoantibody profile in bullous pemphigoid patientsBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2004F. Mariotti Summary Background, The NC16A immunodominant region of the bullous pemphigoid (BP) antigen BP180 has been used to develop several enzyme-linked immunosorbent assays (ELISAs) as diagnostic tools for BP autoantibody detection. Objectives, Because BP180 autoantibody reactivity is not restricted to NC16A, we have investigated the possibility of developing an ELISA based on selected epitopes additional to this immunodominant region. Methods, Initially 78 BP sera were tested using an NC16A ELISA and IgG reactivity was detected in 64 BP sera (82%). The 14 NC16A-negative BP sera were then analysed by immunological screening against seven BP180-specific epitopes. Recombinant phages displaying BP180 epitopes were grown as plaques, blotted onto a nitrocellulose filter and incubated with BP sera. Results, Three and five NC16A-negative BP sera reacted with epitopes AA 1080,1107 and AA 1331,1404 of the BP180 ectodomain, respectively. Thus, a novel ELISA with GST-1080 and GST-1331 (GST-1080/1331) was developed: 32 of 78 BP sera (41%) proved positive by this assay. The combined use of ELISAs with GST-NC16A and GST-1080/1331 detected IgG reactivity in 72 of 78 BP sera, increasing the sensitivity from 82% to 92%. In addition, autoreactivity against the three extracellular epitopes appeared to be related to the presence of both skin and mucosal involvement as assessed by Fisher's exact probability test. Conclusions, Our findings further characterize the autoimmune response in BP by identifying a subgroup of NC16A-negative patients who react with different BP180 extracellular epitopes. The developed ELISA system appears more sensitive than the ELISA based on NC16A alone and also informative about the epitope profile of BP patients. [source] Neonatal pemphigus vulgaris with extensive mucocutaneous lesions from a mother with oral pemphigus vulgarisBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2002A. Campo-Voegeli Summary The clinical phenotype of pemphigus is well explained by the combination of desmoglein (Dsg) 1 and Dsg3 distribution pattern and antiDsg autoantibody profile (Dsg compensation theory). It has been reported that neonatal skin has a similar Dsg distribution pattern to adult mucosal epithelia. We describe a newborn girl with mucocutaneous pemphigus vulgaris (PV) from a mother with mucosal dominant PV. The mother had had painful oral erosions for at least 7 months. Histopathological examination and direct and indirect immunofluorescence studies confirmed the diagnosis of PV and neonatal PV in the mother and daughter, respectively. The mother had a high titre of anti-Dsg3 IgG and a low titre of antiDsg1 IgG, while the neonate had only a high titre of anti-Dsg3 IgG, but no detectable antiDsg1 IgG. AntiDsg3 IgG, which caused the oral dominant phenotype in the mother, induced extensive oral as well as cutaneous lesions in the neonate. Our case provides clinical evidence for the Dsg compensation theory in neonatal PV. [source] AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECEDCLINICAL ENDOCRINOLOGY, Issue 5 2010Sara Cervato Summary Objective, To assess autoimmune regulator (AIRE) gene mutations, class II HLA haplotypes, and organ- or non-organ-specific autoantibodies in patients with chronic hypoparathyroidism (CH) without associated Addison's disease (AD) or chronic candidiasis (CC). Design, Patients and Measurements, Twenty-four patients who had CH without AD or CC were included in the study. AIRE gene mutations in all 14 exons were studied using PCR in 24 patients, 105 healthy controls and 15 first-degree relatives of CH patients with AIRE mutations. Human leucocyte antigens (HLA) were determined for all 24 patients and 105 healthy controls. Autoantibodies to a range of antigens including NACHT leucine-rich-repeat protein-5 (NALP5) and interferon omega (IFN,) were tested in all 24 patients. Results, AIRE gene mutations were found in 6 of 24 (25%) patients, all females, and this was significantly higher (P < 0·001) compared with AIRE mutations found in healthy controls (2/105). Three patients (12·5%) had homozygous AIRE mutations characteristic of Autoimmune-Poly-Endocrinopathy-Candidiasis-Ectodermal-Dystrophy and all three were also positive for IFN,-autoantibodies. Three patients (12·5%) had heterozygous AIRE mutations; two of these were novel mutations. One of the patients with heterozygous AIRE mutations was positive for both NACHT leucine,rich-repeat protein 5 and IFN, autoantibodies. Heterozygous AIRE mutations were found in 10 of 15 first-degree relatives of CH patients with AIRE mutations, although none was affected by CH. Class II HLA haplotypes were not statistically different in patients with CH compared to healthy controls. Conclusions, Analysis of AIRE gene mutations together with serum autoantibody profile should be helpful in the assessment of patients with CH, in particular young women with associated autoimmune diseases. [source] Multiple serological biomarkers for colorectal cancer detectionINTERNATIONAL JOURNAL OF CANCER, Issue 7 2010Chung-Chuan Chan Abstract The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumor-associated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor-associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme-linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY-CO-16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (,5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early-stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer-associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor-associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early-stage patients. [source] Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discoveryPROTEOMICS - CLINICAL APPLICATIONS, Issue 2 2010Joshua W. K. Ho Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune disease that has heterogeneous clinical manifestation with diverse patterns of organ involvement, autoantibody profiles and varying degrees of severity of disease. Research and clinical experience indicate that different subtypes of SLE patients will likely benefit from more tailored treatment regimes, but we currently lack a fast and objective test with high enough sensitivity to enable us to perform such sub-grouping for clinical use. In this article, we review how proteomic technologies could be used as such an objective test. In particular, we extensively review many leukocyte surface markers that are known to have an association with the pathogenesis of SLE, and we discuss how these markers can be used in the further development of a novel SLE-specific antibody leukocyte capture microarray. In addition, we review some bioinformatics challenges and current methods for using the data generated by these cell-capture microarrays in clinical use. In a broader context, we hope our experience in developing a disease specific cell-capture microarray for clinical application can be a guide to other proteomic practitioners who intend to extend their technologies to develop clinical diagnostic and prognostic tests for complex diseases. [source] Distinct subtypes of myelitis in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 11 2009J. Birnbaum Objective Myelitis causes pain, weakness, and sphincteric deficits, and is 1,000-fold more prevalent in patients with systemic lupus erythematosus (SLE) than in the general population. For the last century, descriptions of SLE myelitis have been primarily limited to case reports. In contrast, larger-scale cohort studies have revealed that myelitis occurring in the idiopathic demyelinating diseases (i.e., multiple sclerosis versus neuromyelitis optica) represents distinct syndromes. This study was undertaken to determine whether SLE myelitis similarly encapsulates distinct syndromes. Methods We analyzed a cohort of 22 patients with SLE and myelitis. Patients were assessed for neurologic variables related to myelitis and for clinical and serologic features of SLE. Magnetic resonance images of the spine, cerebrospinal fluid profiles, and autoantibody profiles were obtained. Results Eleven patients presented with signs of gray matter dysfunction (i.e., flaccidity and hyporeflexia), whereas 11 patients presented with signs of white matter dysfunction (i.e., spasticity and hyperreflexia). Patients with gray matter dysfunction were more likely to have irreversible paraplegia (P < 0.01), despite presenting with a monophasic versus polyphasic course (P = 0.01), higher levels of SLE activity (mean SLE Disease Activity Index 9.8 versus 2.0; P = 0.01), and a cerebrospinal fluid profile indistinguishable from bacterial meningitis. Prior to irreversible paraplegia, these patients presented with prodromes of fever and urinary retention, but were misdiagnosed by physicians of different specialties as having urinary tract infections. Patients with white matter dysfunction were more likely to meet criteria for neuromyelitis optica (P = 0.04) and were also more likely to have antiphospholipid antibodies (lupus anticoagulant) (P = 0.01). Conclusion Our findings indicate that SLE myelitis encapsulates 2 distinct and previously unrecognized syndromes that can be distinguished clinically by gray matter versus white matter findings. Recognition of fever and urinary retention as prodromes of irreversible paraplegia may allow earlier diagnosis and treatment in SLE patients presenting with gray matter findings. [source] Opsonization of late apoptotic cells by systemic lupus erythematosus autoantibodies inhibits their uptake via an Fc, receptor,dependent mechanismARTHRITIS & RHEUMATISM, Issue 10 2007Esther Reefman Objective Decreased clearance of apoptotic cells is suggested to be a major pathogenic factor in systemic lupus erythematosus (SLE). The aim of this study was to investigate whether the binding of SLE autoantibodies to apoptotic cells influences the phagocytosis of these cells by macrophages. Methods Apoptosis was induced in a human T cell line (Jurkat) and a keratinocyte cell line (HaCaT) by ultraviolet B irradiation. Binding of purified IgG from 26 SLE patients and 15 healthy controls to apoptotic cells was assessed by flow cytometry and Western blotting. Phagocytosis of IgG-opsonized apoptotic cells by monocyte-derived macrophages was assessed by light microscopy. Similar experiments were performed with a monoclonal antibody against SSA/Ro and IgG fractions from 5 patients with Sjögren's syndrome (SS) and 5 patients with rheumatoid arthritis (RA). Results IgG fractions from all 26 SLE patients bound to late apoptotic, but not early apoptotic, cells. IgG fractions isolated from SLE patients with different autoantibody profiles showed comparable levels of binding. IgG fractions from healthy controls did not bind. Opsonization of apoptotic cells with IgG fractions from SLE patients resulted in a significant inhibition of phagocytosis as compared with healthy control IgG fractions. A monoclonal antibody directed against SSA/Ro and IgG isolated from 5 antinuclear antibody (ANA),positive patients with SS were also able to elicit these effects, whereas IgG from 5 ANA-negative patients with RA did not. The inhibitory effect of patient IgG was abolished by blocking either the Fc, receptors (Fc,R) or the constant region of IgG, using a specific Fc-blocking peptide. Conclusion Autoantibodies from SLE patients are able to opsonize apoptotic cells and inhibit their uptake by macrophages via an Fc,R-dependent mechanism. [source] Arteriographic evaluation of vascular changes of the extremities in patients with systemic sclerosisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2006M. Hasegawa Summary Background, Although digital ulcerations frequently occur in patients with systemic sclerosis (SSc), there have been few reports on the macrovascular involvement. Objectives, To evaluate the macrovascular involvement in patients with SSc exhibiting digital ulceration or gangrene. Methods, Transfemoral catheter arteriography of the upper and/or lower extremities was performed in eight patients (one man and seven women, age range 42,71 years) with SSc exhibiting digital ulceration or gangrene. The background of the patients, such as autoantibody profiles and vascular risk factors including smoking habits, was also investigated. Results, Macrovascular involvement was detected in seven of eight patients. In three of seven patients who underwent arteriography of the upper extremity, occlusion was limited to the digital arteries. Obliteration of the ulnar artery and superficial palmar arch was detected in three of seven patients, and the radial artery in one patient. Only one of five patients who underwent arteriography of the lower extremity showed the occlusion limited to digital arteries of the foot. Occlusion of the posterior tibial artery, dorsalis pedis artery and arcuate artery was detected, each in one patient. Two patients showed occlusion of the plantar arch. Overall, the occlusion of arteries proximal to the digits was demonstrated in four of eight patients. Three of the four patients were positive for antitopoisomerase-1 antibody and had diffuse cutaneous SSc (dcSSc) with multiple skin ulcers or gangrene. Conclusions, Macrovascular involvement as detected with arteriography is not rare in SSc patients with digital ulceration or gangrene. Moreover, the vascular occlusion proximal to the digits seemed to be frequent in antitopoisomerase-1 antibody-positive dcSSc patients with multiple skin ulcers or gangrene. [source] | ||||||||||