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F C Arnett

Publications and source records attributed to F C Arnett.

At least 19 recordsLinked to original sources
PubMed2006

Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients.

OBJECTIVE: To obtain a global view of the immunological alterations occurring in early systemic sclerosis (SSc) by transcriptional profiling of peripheral blood cells (PBCs). METHODS: Oligonucleotide microarrays were used to compare PBC gene expression profiles in 18 SSc cases (<2 yr duration) and 18 controls matched for race, gender and ethnicity. SSc cases had no prior or current exposure to cytotoxic drugs. PAXgene tubes were used to stabilize RNA during phlebotomy. Changes in gene expression were independently validated by real-time polymerase chain reaction. RESULTS: SSc PBCs demonstrated differential expression of 18 interferon-inducible genes. Six of these genes were identical to the interferon signature genes in lupus peripheral blood mononuclear cells. Notably, SSc PBCs also had increased expression of allograft inflammatory factor (AIF1) and several selectins and integrins involved in cellular adhesion to the endothelium. Global analysis of 284 known biological pathways revealed that 13 were differentially regulated in SSc PBCs, including two pathways (IL2RB and GATA3) that lead to T(H)2 polarization. CONCLUSIONS: Transcriptional profiling reliably discriminates between PBCs from SSc and normal donors despite the fact that they represent a heterogeneous cell population. Multiple biological pathways were differentially regulated in SSc PBCs, but a common thread across these pathways was alterations in protein tyrosine kinase 2beta and mitogen-activated protein kinase signalling. Although the SSc PBC gene expression profile demonstrated some parallels with the lupus interferon gene signature, there was also increased expression of transcripts encoding proteins that target PBCs to the endothelium, which might be relevant to the vasculopathy of SSc.

Adult↗
PubMed2006

SPARC, an upstream regulator of connective tissue growth factor in response to transforming growth factor beta stimulation.

OBJECTIVE: To differentiate the effects of inhibition of specific small interfering RNA (siRNA) of SPARC (secreted protein, acidic and rich in cysteine) and siRNA of connective tissue growth factor (CTGF) in cultured human fibroblasts, and to identify potential interrelationships between SPARC and CTGF. METHODS: Fibroblasts from skin biopsy specimens of 2 normal individuals were transfected with siRNA of SPARC and siRNA of CTGF. The fibroblasts were stimulated with or without transforming growth factor beta1 (TGFbeta1) and examined by real-time quantitative reverse transcription-polymerase chain reaction to determine the transcription levels of several extracellular matrix genes. RESULTS: After exogenous TGFbeta1 stimulation, both SPARC siRNA and CTGF siRNA showed a protective role against overexpression of collagen genes. Following TGFbeta1 stimulation, SPARC siRNA-transfected fibroblasts showed a greater reduction in expression of the collagen genes compared with CTGF siRNA-transfected fibroblasts, as well as a significantly decreased expression of CTGF (P < 0.05). Using linear structure equations to quantitatively model a genetic network based on expression levels of each gene, a positive regulatory role of SPARC on CTGF, COL1A2, COL3A1, COL11A1, and TIMP3 was observed. However, the regulatory role of CTGF on SPARC appeared to be negative and very small, while the positive regulatory effects of CTGF on COL1A2, COL3A1, COL11A1, and TIMP3 were less than those of SPARC. CONCLUSION: The results of this quantitative comparison support the hypothesis that in these cultured fibroblasts, the regulatory effects of SPARC on some major extracellular matrix structural components are greater than those of CTGF. In addition, SPARC appears to regulate CTGF in a predominantly positive manner, while CTGF may act as a negative feedback control on SPARC following TGFbeta stimulation.

Cells, Cultured↗
PubMed2004

Intra- and intercontinental molecular variability of an Alu insertion in the 3' untranslated region of the LDLR gene.

One-hundred three individuals from two Mongolian, two Siberian, and ten native American populations were studied in relation to a 340-bp sequence from an Alu insertion located in the 3' untranslated region of the LDLR gene. Seven haplotypes have been determined, and haplotype B1 was the most common, accounting for about half the sequences found. In general, diversity values are quite high, about 2.5 times higher than those found in other autosomal Alu sequences. Almost all (93%) of the variability occurs at the intrapopulation level, but the greatest among-group differentiation (6-8%) was found when we grouped in a single population all Native Americans plus Siberian Eskimos and Chukchi and compared them with Mongolians. This result is compatible with earlier mtDNA and Y-chromosome suggestions of a single origin for the first colonizers of the American continent. With this nuclear locus it was not possible to broadly distinguish between Central and South American natives. No evidence of selection or marked demographic changes was obtained with these data.

3' Untranslated Regions↗
PubMed2003

Sulfatides: targets for anti-phospholipid antibodies.

BACKGROUND: Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. Beta2-glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether beta2-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies. METHODS AND RESULTS: Beta2-glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 microg/well, beta2-glycoprotein I reaches half-maximal binding at 2.5 microg/mL, and the binding is saturated at 10 microg/mL. The binding of beta2-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant beta2-glycoprotein I concentration of 5 microg/mL, maximal binding of beta2-glycoprotein I is observed at a coating density of 1 mug/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound beta2-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-beta2-glycoprotein I complex by >50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound beta2-glycoprotein I. CONCLUSIONS: These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome.

Antibodies, Anticardiolipin↗
PubMed2001

Systemic sclerosis (scleroderma): specific autoantigen genes are selectively overexpressed in scleroderma fibroblasts.

The pathogenesis of systemic sclerosis (SSc) involves complex interactions between activated fibroblasts eventually leading to fibrosis, and impaired immune tolerance characterized by a variety of circulating SSc-specific autoantibodies. The expression of autoantigens in fibroblasts, a key target tissue in SSc, may play an important role in this process. To obtain a global view of this process, we examined gene expression profiles of SSc dermal fibroblasts using cDNA microarrays. The results show that dermal fibroblasts from SSc patients obtained from either affected or unaffected skin displayed a characteristic pattern of increased SSc autoantigen gene expression compared with that from normal controls. In particular, fibrillarin (p = 0.028), centromeric protein B (p = 0.01), centromeric autoantigen P27 (p = 0.042), and RNA polymerase II (220 kDa; p = 0.02) were significantly overexpressed in SSc fibroblasts. Quantitative RT-PCR confirmed overexpression of these autoantigens and also revealed increased levels of DNA topoisomerase I transcripts in SSc fibroblasts compared with normal control fibroblasts (p = 0.0318). The polymyositis/scleroderma autoantigen gene was overexpressed in some SSc patients (p = 0.09). To examine the specificity of these overexpressed autoantigen genes for SSc and its tissue specificity for fibroblasts, cDNA microarrays of dermal fibroblasts from patients with eosinophilic fasciitis and scleromyxedema were studied as well as PBMC and muscle biopsies from SSc patients. None of these tissues showed significant alterations in gene expression of SSc-specific autoantigens. Therefore, SSc-associated autoantigen genes are selectively overexpressed in SSc dermal fibroblasts, a major tissue involved in disease pathogenesis.

Autoantigens↗
PubMed2001

A fatal case of Vibrio vulnificus presenting as septic arthritis.

Vibrio vulnificus is an invasive gram-negative bacillus that may cause necrotizing cellulitis, bacteremia, and/or sepsis. Although V vulnificus infection is uncommon, it is frequently fatal and is usually attributed to ingestion of raw shellfish or traumatic exposure to a marine environment; patients are also often found to have a hepatic disorder (cirrhosis, alcohol abuse, or hemochromatosis) or an immunocompromised health status, and most commonly present with septicemia or a wound infection. We describe a patient who presented with septic arthritis as the first clinical manifestation of a V vulnificus infection. The organism was subsequently identified in a synovial fluid aspirate.

Arthritis, Infectious↗
PubMed2001

Association of fibrillin 1 single-nucleotide polymorphism haplotypes with systemic sclerosis in Choctaw and Japanese populations.

OBJECTIVE: Previously, we demonstrated with the use of microsatellite markers that a 2-cM haplotype on chromosome 15q containing the fibrillin 1 gene (FBN1) was strongly associated with systemic sclerosis (SSc) in the Choctaw, a population with high SSc prevalence. In this study, all 69 known FBN1 exons were sequenced to ascertain the presence of changes that might show associations with SSc in the Choctaw and Japanese SSc patients and controls. METHODS: Screening of FBN1 exons was accomplished by polymerase chain reaction-based fluorescence sequencing of genomic DNA using single-nucleotide polymorphism (SNP) haplotypes, and their frequencies were determined with a new algorithm that recognizes past recombination events between sites. Haplotype phylogenies were inferred using the median-joining network analysis. RESULTS: Five SNPs were identified in FBN1. They are located in the 5'-untranslated region (SNP-1), exon 15 (SNP-2), intron 17 (SNP-3), exon 27 (SNP-4), and intron 27 (SNP-5). Only SNP-1 (T-->C) demonstrated an association with SSc in the Choctaw. Eleven FBN1 SNP haplotypes were ascertained in the Choctaw population, 2 of which (SNPs 5 and 6) were found only in the SSc patients. These same FBN1 SNP haplotypes were associated with SSc in the Japanese. CONCLUSION: A SNP in the 5'-untranslated region of FBN1 (SNP-1, C allele) was strongly associated with SSc in the Choctaw. Furthermore, this polymorphism is present on 2 unique FBN1 haplotypes found only in Choctaw SSc patients. The same 2 haplotypes demonstrate associations with SSc in the Japanese. These data extend the earlier microsatellite studies and are consistent with the hypothesis that FBN1 or a nearby gene on chromosome 15q is involved in SSc susceptibility in the Choctaw and the Japanese.

5' Untranslated Regions↗
PubMed2001

Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts.

OBJECTIVE: To determine the frequency with which scleroderma (systemic sclerosis; SSc) recurs in families and the familial relative risk (lambda) in the US. METHODS: Family histories of SSc were prospectively surveyed in 3 large US cohorts of SSc patients, 2 in Texas and 1 in Michigan. Diagnoses of familial SSc were verified by rheumatologist evaluation and/or review of medical records. Familial relative risks for first-degree relatives (lambda1) and siblings (lambdas) were calculated using actual reported counts of first-degree relatives in 2 cohorts and recent estimates of SSc prevalence in the US. RESULTS: Compared with the estimated prevalence of SSc in the US (2.6 cases/10,000 population [0.026%]), the disease occurred in 1 or more first-degree relatives in 1.5-1.7% of SSc families in the 3 cohorts (or 11 of 703 families [1.6%]), a significant increase. Familial relative risks in first-degree relatives in the 3 cohorts ranged from 10 to 16 (13 combined), and in siblings they ranged from 10 to 27 (15 combined). CONCLUSION: SSc occurs significantly more frequently in families with scleroderma (1.6%) than in the general population (0.026%). A positive family history of SSc is the strongest risk factor yet identified for SSc; however, the absolute risk for each family member remains quite low (<1%).

Black People↗
PubMed2001

Abnormalities in fibrillin 1-containing microfibrils in dermal fibroblast cultures from patients with systemic sclerosis (scleroderma).

OBJECTIVE: To determine if there are abnormalities in fibrillin 1-containing microfibrils in the extracellular matrix (ECM) of primary dermal fibroblasts explanted from patients with systemic sclerosis (SSc). METHODS: Explanted fibroblasts from unaffected skin of 12 SSc patients were used to examine fibrillin 1-containing microfibrils by immunofluorescence (IF) using a monoclonal antibody (mAb) to fibrillin 1. Metabolic labeling of the fibroblast cultures was used to study the synthesis, secretion, and processing of fibrillin 1, as well as to observe microfibril formation and stability. Microfibrils elaborated by the SSc cells were analyzed by electron microscopy for ultrastructural abnormalities, and the results were confirmed by immunoblotting. RESULTS: Control and SSc fibroblasts displayed a prominent meshwork of fibrillin 1-containing microfibrils when visualized by IF using a fibrillin 1 mAb. Paradoxically, metabolic studies indicated a paucity of fibrillin 1 in the ECM in the majority of the SSc fibroblast strains. Subsequent rotary-shadowed electron microscopy revealed reduced amounts of and ultrastructural abnormalities in the microfibrils elaborated by all strains of SSc cells. Immunoblots confirmed the lack of the high molecular weight form of fibrillin 1 in the SSc fibroblasts of Choctaw American Indians. Finally, in vitro studies indicated that the amount of fibrillin 1 in the ECM of SSc cells diminished at a faster rate than the amount of fibrillin 1 in the ECM of control cells with time. CONCLUSION: Although SSc fibroblasts assemble microfibrils, these microfibrils are unstable, suggesting that an inherent defect of fibrillin 1-containing microfibrils may play a role in the pathogenesis of SSc.

Adult↗
PubMed2001

Glutathione S-transferase genotypes in systemic sclerosis and their association with clinical manifestations in early disease.

The glutathione S-transferases (GSTs) are a family of enzymes involved in limiting oxidative damage to tissues. Null alleles for one or more of the GST enzymes, especially GSTM1, reportedly occur more frequently in patients with Sjögren's syndrome and systemic lupus erythematosus who possess certain autoantibodies. Because systemic sclerosis (SSc) is a disease in which oxidative damage has been hypothesized to contribute both to immune dysfunction and tissue damage, we sought to determine if patients from a multi-ethnic cohort of SSc patients with early disease (< or =5 years) were more likely than ethnically-matched normal controls to have null alleles for GSTM1 (M1) and/or GSTT1 (T1), and if the null allele status correlated with any major disease features. The data show that while M1 and T1 null genotypes were not significantly increased in SSc compared to ethnically matched controls, their frequencies (especially T1 nulls) were significantly higher among SSc patients with hypertension and pulmonary involvement. This suggests that GST genotype may be a genetic factor that contributes to clinical disease expression in SSc.

Genotype↗
PubMed2001

Lack of association of a functionally relevant single nucleotide polymorphism of matrix metalloproteinase-1 promoter with systemic sclerosis (scleroderma).

Matrix metalloproteinase 1 (MMP-1) is necessary for degradation of interstitial collagen types I, II, and III, which are the major constituents of the extracellular matrix (ECM). Increased expression of MMP-1 has been correlated with invasiveness of certain malignancies and cartilage degradation in rheumatoid arthritis. Increased transcriptional activity of MMP-1 has been reported with a single nucleotide polymorphism (SNP) of the MMP-1 promoter. Systemic sclerosis (SSc) is characterized by increased accumulation and turnover of collagen and other components of ECM. Previous studies have reported increased expression of MMP-1 transcripts in SSc fibroblasts. Therefore, we sought to determine if SSc patients with early disease (< or =5 years) from a multi-ethnic cohort were more or less likely than ethnically-matched normal controls to have an increased frequency of the high promoter activity MMP-1 genotype and whether MMP-1 promoter genotypes correlated with any of the major clinical manifestations of SSc. The results show that the frequency of the high activity promoter genotype in either the heterozygous or homozygous state did not differ significantly between SSc patients and ethnically-matched controls, or between SSc patients with either diffuse or limited scleroderma. Furthermore, MMP-1 promoter genotypes did not significantly correlate with any of the major clinical manifestations of SSc.

Humans↗
PubMed2001

Systemic sclerosis in 3 US ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants.

OBJECTIVE: To determine whether ethnic factors influence the presentation, serologic expression and immunogenetics of systemic sclerosis (SSc), patients from 3 ethnic groups were compared for clinical features, SSc-associated autoantibodies, and human leukocyte antigen (HLA) class II alleles. METHODS: Fifty-four Hispanics, 28 African Americans, and 79 whites from Texas with recent-onset (less than 5 years) SSc enrolled in a prospective longitudinal study were assessed for sociodemographic, clinical, immunologic, immunogenetic, behavioral, and psychologic parameters using validated instruments and standard laboratory techniques. Serologic and immunogenetic characteristics from these patients and larger retrospective SSc cohorts of the same ethnic groups also were examined. RESULTS: Hispanics and African Americans in the prospective cohort were more likely to have diffuse skin involvement, skin pigmentary changes, digital ulcers, pulmonary hypertension (African Americans), and an overall lower sociodemographic status than whites, who had more facial telangiectasia and hypothyroidism. In the larger combined prospective and retrospective groups of SSc patients, whites were likely to have more anticentromere antibodies (ACA) and African Americans more anti-U1-ribonucleoprotein (RNP) and anti-U3-RNP (fibrillarin) autoantibodies. HLA-DQB1*0301 was significantly associated with SSc per se in all 3 ethnic groups; HLA-DRB1*11 correlated with the anti-topoisomerase I antibody response, and HLA-DRB1*01, DRB1*04, and DQB1*0501 with ACA. CONCLUSIONS: Important sociodemographic, clinical, and serologic differences exist between whites, African Americans, and Hispanics, despite shared genetic (HLA class II) predisposing factors. The impact of these differences on prognosis remain to be determined.

Adult↗
PubMed2000

Primary antiphospholipid antibody syndrome with mutations in the phospholipid binding domain of beta(2)-glycoprotein I.

beta(2)-Glycoprotein I, an anionic phospholipid-binding 50-kDa plasma protein, circulates in the plasma at a concentration of 30-200 microg/ml. Its physiological role remains uncertain, but an important clue to this role is suggested by the finding that antibodies to this protein are frequently found in patients with antiphospholipid antibodies and thrombosis. beta(2)-Glycoprotein I belongs to the complement control protein (CCP) superfamily with five CCP domains. The fifth CCP domain of beta(2)-glycoprotein I has a unique structure and contains a stretch of positively charged amino acids that mediates the binding to phospholipids. This interaction may mediate the clearance of anionic phospholipid-containing surfaces from the circulation. Mutations in this domain affect its binding to phospholipids. We have identified a patient with primary antiphospholipid syndrome who is a compound heterozygous for two mutations in the fifth CCP. One mutation is located in exon 7 (codon 306), and the second mutation is in exon 8 (codon 316). The mutant beta(2)-glycoprotein I was present in normal quantities in his plasma but did not bind to cardiolipin. He had recurrent deep vein thrombosis and pulmonary embolism at age 28 and a thrombotic stroke at age 35, with no other identifiable risk factor for a hypercoagulable state. This report offers some insight into the mechanism of formation of antiphospholipid antibodies and suggests the possible role of the deficiency of beta(2)-glycoprotein I in the pathogenesis of thrombosis.

Adult↗
PubMed2000

Microsatellites and intragenic polymorphisms of transforming growth factor beta and platelet-derived growth factor and their receptor genes in Native Americans with systemic sclerosis (scleroderma): a preliminary analysis showing no genetic association.

OBJECTIVE: Abnormalities of transforming growth factor beta (TGFbeta) and platelet-derived growth factor (PDGF) alpha and beta and/or their receptors have been demonstrated in systemic sclerosis (SSc). This study aimed to determine whether genetic polymorphisms in or near the TGFbeta and PDGF gene families were associated with susceptibility to SSc in a Native American population with a high disease prevalence. METHODS: Genotyping of 5 intragenic polymorphisms within the TGFbeta1 gene and mapping of 35 microsatellites near the genes for TGFbeta1, latent TGFbeta1 binding protein (LTBP1), TGFbeta receptors I and II, PDGFalpha, PDGFbeta, PDGF receptor alpha, and PDGF receptor beta was performed in 19 SSc patients, 76 controls, and 42 family members. Allele distributions and frequencies were examined between SSc patients and controls, and marker haplotypes were examined in families when allele frequencies appeared to be different between patients and controls. RESULTS: Although 1 polymorphism within the TGFbeta1 gene (TGFbeta1) was modestly increased in the SSc patients, this did not maintain statistical significance after correction. Similarly, 1 microsatellite (D9S120) near the TGFbeta receptor I gene (TGFBR1) showed a significant disturbance of allele frequencies between patients and controls; however, it did not form a disease-associated haplotype with other nearby markers. Weak disturbances of markers near PDGFalpha (PDGFA) and PDGFbeta, (PDGFB) also failed to maintain significance after correction. Both PDGF receptor genes (PDGFRA and PDGFRB) also showed no disease associations. CONCLUSION: The results of these preliminary analyses suggest that genetic anomalies of the TGFbeta1 and PDGF gene families are not likely to explain the dysregulation seen in SSc or to account for the susceptibility to SSc in this population.

Alleles↗
PubMed2000

Autoantibodies to fibrillin 1 in systemic sclerosis: ethnic differences in antigen recognition and lack of correlation with specific clinical features or HLA alleles.

OBJECTIVE: We previously reported the presence of autoantibodies to the extracellular matrix protein, fibrillin 1, in sera from patients with systemic sclerosis (SSc). These autoantibodies appeared to be highly disease-specific but had significantly different frequencies among ethnic groups. The aims of this study were 3-fold: 1) to determine whether sera from SSc patients of different ethnic backgrounds recognized different antigenic epitopes of fibrillin 1, 2) to determine whether sera from patients with polymyositis/dermatomyositis (PM/DM) with or without interstitial lung disease (ILD) also produced these antibodies, and 3) to determine any correlation of anti-fibrillin 1 antibodies with specific clinical features of SSc, other autoantibodies, or HLA class II alleles in a prospectively studied cohort of SSc patients with early (<5 years' duration) disease (the Genetics versus Environment In Scleroderma Outcome Study [GENISOS] cohort). METHODS: Three recombinant peptides accounting for the N-terminal end, proline-rich C region, and epidermal growth factor-like calcium-binding (EGF-cb) domains of fibrillin 1 were used in a radioimmunoassay to screen sera from a large group of SSc and PM/DM patients and ethnically matched controls. RESULTS: The majority of Choctaw American Indians, Japanese, and African Americans with SSc produced IgM and/or IgG autoantibodies to one or more recombinant fibrillin 1 proteins, while <50% of Caucasians with SSc showed seroreactivity. There were striking ethnic differences in fibrillin 1 antigenic epitope recognition among these ethnic groups. African American SSc sera recognized primarily the N-terminal end, and Caucasian sera mostly recognized the EGF-cb repeats and the proline-rich C region. In contrast, most Choctaw American Indian and Japanese SSc sera appeared to recognize 2 or 3 epitopes, respectively. PM/DM patient sera did not recognize any of the fibrillin 1 epitopes regardless of the presence of ILD. In the prospective, multiethnic GENISOS cohort, the presence of anti-fibrillin 1 antibodies did not correlate with any major clinical manifestations, other autoantibodies, or HLA class II alleles. CONCLUSION: There are striking ethnic differences in antigenic epitope specificity of anti-fibrillin 1 antibodies in patients with SSc, and the majority of SSc patients, except for Caucasians, produce antibodies to fibrillin 1. The antifibrillin response thus far remains specific for scleroderma syndromes, but it does not correlate with any major clinical features, other autoantibodies, or HLA class II alleles.

Alleles↗
PubMed2000

Unique epitopes in RNA helicase II/Gu protein recognized by serum from a watermelon stomach patient.

RNA helicase II/Gu (RH II/Gu) is a nucleolar antigen originally identified using an autoimmune serum from a patient with watermelon stomach. A later report showed that anti-RH II/Gu autoantibodies were also present at low frequency in connective tissue disease (CTD) patients who did not show any symptoms suggestive of a watermelon stomach lesion. In an attempt to understand the relationship between watermelon stomach, also called gastric antral vascular ectasia (GAVE), and autoimmune disorder, we identified the antigenic sites recognized by these autoantibodies. Serum Gu uniquely recognized epitopes at amino acids 646-748 of RH II/Gu and all four CTD patient sera recognized antigenic sites within amino acids 1-173. Anti-RH II/Gu serum produced by immunizing rabbit with recombinant human RH II/Gu protein bound to the same antigenic sites recognized by the CTD patient sera, but it did not recognize the serum Gu epitopes. Results are also presented showing the use of these anti-RH II/Gu antibodies in the analysis of the evolutionary conservation of RH II/Gu in human, monkey and mouse.

Amino Acid Sequence↗