Antigen B27 Research Articles

Cross-staining of cytotoxic T lymphocyte populations with peptide-MHC class I multimers of natural HIV-1 variant antigens.

Multimeric soluble peptide-MHC class I complexes bind to T cell receptors (TCR) on the surface of CD8 cytotoxic T lymphocytes (CTL) with sufficient avidity to enable the labelling of CTL according to their antigen specificity [1]. Visualization of antigen-specific CD8+T lymphocytes with fluorogen-conjugated peptide-MHC class I multimers enables both the physical quantification and the phenotypic characterization of CTL responses directly ex vivo, and these properties have led to the widespread adoption of this technique throughout the field of experimental immunology. However, it is well documented that TCR can exhibit a degree of promiscuity in terms of ligand recognition [2]. We recently demonstrated that the multimerization of peptide-MHC class I can allow binding to TCR with affinities that are too low to generate ligand-induced physiological responses, and result in crossreactive staining of HIV-specific CTL lines and clones by unrecognized natural variant antigens [3]. These results suggest that crossreactivity between peptide-MHC class I multimers and low avidity CTL could be relevant to the interpretation of direct ex-vivo staining. The possibility of such cross-staining is likely to be considerably greater when using peptide-MHC class I multimers to stain CTL specific for epitopes derived from antigenically variable pathogens such as HIV-1 [4]. Here we extend our previous study with the demonstration that the cross-staining of CTL populations with peptide-MHC class I multimers can complicate analyses performed directly ex vivo.

High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction.

Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects. Age and body mass index were similar in the two groups. Nine of the 13 patients had hypergonadotropic hypogonadism (five of whom had Klinefelter's syndrome [karyotype 47,XXY]) and 4 of the 13 had hypogonadotropic hypogonadism (46,XY). Of these last four, two had Kallmann's syndrome and two had idiopathic cryptorchidism. Eight (61%) of the 13 patients studied had RADs unrelated to the etiology of their hypogonadism. Of these, four had ankylosing spondylitis and histocompatibility B27 antigen, two had systemic lupus erythematosus (in one case associated with antiphospholipids), one had juvenile rheumatoid arthritis, and one had juvenile dermatomyositis. In comparison with the low frequencies of RADs in the general population (about 0.83%, including systemic lupus erythematosus, 0.03%; dermatomyositis, 0.04%; juvenile rheumatoid arthritis, 0.03%; ankylosing spondylitis, 0.01%; rheumatoid arthritis, 0.62%; and other RAD, 0.1%), there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P < 0.001) and very low serum testosterone levels (P = 0.0005). The presence of RADs in these patients was independent of the etiology of their hypogonadism and was associated with marked gonadal failure with very low testosterone levels.

Strong association of HLA-B27 heavy chain with β 2-microglobulin

Monoclonal antibody TG1 recognizes specifically antigens HLA-B27, B7, B22 and B17 on cell surface in cytotoxicity and cytofluorometry tests. When cell detergent extracts were subjected to SDS PAGE under mild conditions (no heating and no reduction of the sample) followed by Western blotting, TG1 detected exclusively a complex of B27 heavy chains with β 2-microglobulin (as a 50 kDa band) whereas the other B-locus antigens (B7, B22, B17) were detected as free 43 kDa heavy chains under the same conditions. When the samples were boiled prior to SDS PAGE, TG1 detected again the 43 kDa free heavy chains of B7, B22 and B17 but no zone corresponding to B27 could be detected indicating that the epitope in free B27 chains is more sensitive to denaturation by SDS. Thus, our main finding is that the interaction of HLA-B27 heavy chain with β 2-microglobulin appears to be stronger than that of the other HLA-B chains. The resistance of the HLA-B27/β 2-microglobulin complex to the SDS dissociation is strikingly similar to the behavior of MHC class II molecules under similar conditions. Thus, it may be speculated that HLA-B27 complexes can be also more stable than other MHC class I molecules under more physiological dissociative conditions (e.g. in endosomal compartments). This feature might potentially influence antigen presentation by HLA-B27 and contribute to the well known disease linkage of HLA-B27.

Can some cases of ‘possible’ spondyloarthropathy be classified as ‘definite’ or ‘undifferentiated’ spondyloarthropathy?Value of criteria for spondyloarthropathies

Objectives. When evaluating patients for spondyloarthropathy, clinicians use the ‘possible spondyloarthropathy’ category to indicate that they are unsure about the diagnosis. We sought to determine whether Amor’s criteria or the European Spondyloarthropathy Study Group (ESSG) criteria could lift this uncertainty. Patients and methods. During a Spanish study designed to validate criteria for spondyloarthropathies, 102 patients were classified in the ‘possible spondyloarthropathy’ category. We divided these patients into subgroups based on whether or not they met criteria for spondyloarthropathy. We compared baseline characteristics ( N = 102) and five-year outcomes ( N = 52) in these subgroups. Results. The following features were significantly more common in the subgroups of patients who met Amor’s criteria for spondyloarthropathy: oligoarthritis, heel pain, uveitis, balanitis, family history of spondyloarthropathy, and presence of the HLA B27 antigen. No differences were found for age at symptom onset, disease duration, buttock pain, gender, dactylitis, diarrhea, or psoriasis. Of the 52 patients followed up for five years, 17 met Amor’s criteria at baseline and 13 were subsequently found to have definite spondyloarthropathy, which was undifferentiated in six cases. There were only three cases of spondyloarthropathy among the 28 patients who did not meet Amor’s criteria at baseline. Of the 28 patients who met ESSG criteria at baseline, 13 had spondyloarthropathy versus three of the 17 patients who did not meet ESSG criteria at baseline. Conclusion. Amor’s criteria or the ESSG criteria allow early classification of most patients with ‘possible spondyloarthropathy’ and early identification of undifferentiated spondyloarthropathy corresponding to minimal-symptom or incipient disease. In this study, Amor’s criteria performed better than the ESSG criteria.

A common HLA phenotype in slipped capital femoral epiphysis?

Studies from three different countries have linked the HLA B12 and DR4 antigens with slipped capital femoral epiphysis (SCFE). We questioned whether our patients shared in common either of these antigens. HLA phenotype was determined in 7 patients with SCFE, two of whom were brothers with almost identical haplotypes. The B12 antigen was found in none of our patients and the DR4 in only 3. Neither of the 2 brothers held the DR4 antigen. The commonest antigens (also shared by the 2 brothers) were B35, present in 5 and DR52 in 4 of 7 patients. We conclude that neither the previously described B12 nor the DR4 antigen can reliably serve as genetic markers for SCFE in our region.

Prevalence of hla antigens and haplotypes in noncaucasian transplant patients with autoimmune hepatitis

Background: Autoimmune hepatitis (AIH) is a chronic necroinflammmatory liver disease that affects mainly young caucasian women. HLA antigens AI, B8, DR3 and DR4 have been associated with different clinical presentations of AIH in caucasian (C) patients. The prevalence of these antigens is unknown in other ethnic groups with AIR. Aim: Evaluate the prevalence of HLA antigens AI, B8, DR3 and DR4 in noncaucasian (NC) patients with autoimmune hepatitis. Methods:We reviewed the records of 37 patients undergoing liver transplantation (OLT) for AIH between June 1994 and March 1999. HLA antigens were determined serologically by Standard Lymphocytotoxicity Method (one Lambda Canuga Park LA). The HLA of these patients were compared to 115 liver transplant donors as controls. Results: Out of the 37 AIH patients who underwent OLT, 20 were C and 17 were NC. NC patients included: 5 Hispanics (H) and 12 Blacks (B).Among donors, 46 were C and 69 were NC. NC donors included: 58 H, 10 Band 1 Asian. The prevalence of HLA antigens AI, B8, DR3 and DR4 in AIH patients was not different between C and NC. However 6 of 20 C had haplotype AIB8DR3 or AIB8DR4 vs none of 17 NC (p=0.014). When C patients were compared with C controls the prevalence of B8 (8120 vs 4/46) and DR3 (7/20 vs 2/46) was statistically significant (p=0.0047 and 0.0023 respectively). No other known or expected HLA antigens or haplotypes were significantly increased in C pts when compared to C controls. In NC pts however, the prevalence of AI, B8, DR3 and DR4 were not different than NC controls. The prevalence of A30 (6/17 vs 7/69, p=0.018), A31 (2/17 vs 0/69, p=0.037), and B42 (3/17 vs 1/68, p=0.02) was increased in NC patients when compared to NC controls. 4 out of 6 patients wiht A30, both patients with A31, and 2 out of 3 patients with B42 were black, which is a common finding. Conclusion: The increased prevalence of HLA B8, and DR3 antigens, and HLA AIB8DR3 and HLA AIB8DR4 haplotypes in caucasian patients was in agreement with previous reports. In noncaucasian patients with AIH there was no increase in these HLA antigens or haplotypes. HLA A30, A31 and B42 were more prevalent in noncaucasian patients with AIR.

B7 expression and antigen presentation by human brain endothelial cells: requirement for proinflammatory cytokines.

Interaction between systemic immune cells with cells of the blood-brain barrier is a central step in development of CNS-directed immune responses. Endothelial cells are the first cells of the blood-brain barrier encountered by migrating lymphocytes. To investigate the antigen-presenting capacity of human adult brain endothelial cells (HBECs), we used HBECs derived from surgically resected temporal lobe tissue, cocultured with allogeneic peripheral blood derived CD4+ T lymphocytes. HBECs in response to IFN-gamma, but not under basal culture conditions, expressed HLA-DR, B7.1 and B7.2 antigens. Despite such up-regulation, these IFN-gamma-treated HBECs, in contrast to human microglia and PB monocytes, did not sustain allogeneic CD4+ cell proliferation, supported only low levels of IL-2 and IFN-gamma production, and did not stimulate IL-2 receptor expression. CD4+ T cell proliferation and increased IL-2 receptor expression could be obtained by addition of IL-2. Our data suggests that, although HBECs cannot alone support T cell proliferation and cytokine production, HBECs acting in concert with cytokines derived from a proinflammatory environment could support such a response.

Identification of an HLA-B7 serological variant and its characterization by sequencing based typing.

We have identified an HLA-B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence-specific primers (PCR-SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti-HLA antisera, gave disparate results for the B antigens. Monoclonal antibodies identified B7 and B8 antigens but polyclonal antisera recognised only the B8 antigen. PCR using sequencing based typing (PCR-SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA-B*07 allele was isolated by allele-specific PCR and was shown to have a mutation, G-->T, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 antigen-specific epitope recognised by tissue typing polyclonal antisera.

Prospective Analysis after Coronary-artery Bypass Grafting: Platelet GP IIIa Polymorphism (HPA-1b /PlA2) Is a Risk Factor for Bypass Occlusion, Myocardial Infarction, and Death

Recently, we have demonstrated that human platelet antigen 1b (HPA-1b or P1A2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-lb does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-lb on the outcome in patients after coronary-artery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronary-artery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-lb was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA-1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-lb had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.

Significant associations of HLA-B*5101 and B*5108, and lack of association of class II alleles with Behçet's disease in Italian patients.

Behçet's disease has been known to be strongly associated with human leukocyte antigen (HLA) B51, one of the split antigens of HLA-B5. An increased incidence of HLA-B51 in the patient group has also been reported in an Italian population. Since the B51 antigen has been recently identified to comprise nine alleles, B*5101-B*5109, we performed HLA-B51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method as well as serological HLA-A and -B typing among 21 Italian patients with Behçet's disease in order to investigate whether there is any correlation of one particular B51-associated allele with Behcet's disease. In addition, HLA class II genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. As a result, only the phenotype frequency of the B51 antigen was found to be significantly increased in the patient group as compared to the ethnically matched control group by the corrected P-value analysis (71.4% in patients vs. 17.9% in controls; chi2 = 14.26, Pc = 0.0042, R.R. = 11.5). In the B51 allele genotyping, 11 out of 15 B51-positive patients were B*5101 and the remaining four were B*5108, whereas all of 5 normal controls were B*5101, showing significant association of each allele with Behçet's disease. No significant difference was observed between the patient and control groups in the HLA class II allelic distribution. This study revealed a strong association of Behçet's disease in Italian with B*5108 as well as B*5101, providing important insight into the molecular mechanism underlying an HLA association with Behçet's disease.

SAPHO syndrome: A long-term follow-up study of 120 cases

Objective: To assess the long-term outcome of the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Methods: All patients with the SAPHO syndrome seen at our unit between 1974and 1997 were identified. Follow-up was prospective from 1992 to 1997. Data before 1992 were analyzed retrospectively. Clinical symptoms, treatments and biological data, including erythrocyte sedimentation rate and C-reactive protein, were recorded at least yearly. When available, radiological data, HLA B27 status, and findings from bone or skin biopsy specimens were recorded. For each drug, an efficacy index (EI) was determined as follows: “0” for less than 30% improvement, as judged by the patient, on horizontal visual analog scale, “0.5” for partial efficacy, and “1” for more than 60% improvement. Results: We identified 120 patients with the SAPHO syndrome (50 men, 70women), of whom 102 patients were followed-up prospectively after 1992; 3 of these 102 patients were lost to follow-up. Six patients also had Crohn's disease, and three had ulcerative colitis. Except for a significant association of palmoplantar pustulosis (PPP) or psoriasis vulgaris (PV) with axial osteitis ( P = .007), the dermatologic presentation had no significant influence on rheumatic symptoms (ie, osteitis or arthritis, peripheral or axial). The HLA B27 antigen was not significantly associated with a particular pattern of distribution of arthritis or osteitis. No severe or disabling complications were noted. In the 47 patients followed-up for more than 5 years (mean, 9.5; range, 5 to 23), the mean number of osteitis or arthritis foci increased during follow-up from 1.57 to 1.91 and from 2.68 to 3.11, respectively. Nonsteroidal antiinflammatory drugs (NSAIDs) were prescribed in 113 of 120 (94%) patients, with a mean El of 0.67 (±0.39). Corticosteroid (CS) therapy was used in 23 patients, with a mean El of 0.67 (±0.42). Colchicine and sulfasalazine had a mean El of 0.36 (±0.44) and 0.16 (±0.30), in 28 and 18 patients, respectively. Methotrexate was given to 10 patients (6 with peripheral arthritis), with a mean El of 0.64 (±0.48). Doxycyclin (100 mg twice daily) was used in 20 patients, usually to treat osteitis, with a mean El of 0.26 (±0.42). Intraarticular injections of a CS or osmic acid were used in 27 patients, with a mean El of 0.77 (±0.35). Conclusions: SAPHO syndrome is a relevant and stable entity, with a good long-term prognosis. NSAIDs and intraarticular injections (CS or osmic acid)

Adult linear IgA disease and chronic bullous disease of childhood: the association with human lymphocyte antigens Cw7, B8, DR3 and tumour necrosis factor influences disease expression

Linear IgA disease and chronic bullous disease of childhood are both subepidermal autoimmune blistering diseases. Class I and II major histocompatibility locus (MHC) antigen typing was performed on 60 patients (26 chronic bullous disease of childhood, 34 adult linear IgA disease), and the findings were correlated with the clinical course. The typing was performed using a lymphocyte microcytotoxicity assay, and the results were compared with a reference population of U.K. organ donors. Analysis of the tumour necrosis factor (TNF) locus was performed using sequence-specific oligonucleotides on a dot blot in 51 patients and compared with a random control population and human lymphocyte antigen (HLA) DR3 matched controls. The disease was found to be significantly associated with HLA Cw7 (chi2 = 19.24, P = 0.001), B8 (chi2 = 9.89, P = 0.04) and DR3 (chi2 = 10.47, P = 0.014), all components of the common Caucasian haplotype. There was also a close association between the disease and possession of HLA DR2 or 3 (chi2 = 16.34, P = 0.001). A reduction in the incidence of DR1 and DR4 (alleles carrying the rheumatoid motif) was observed, which is more marked in the children (chi2 = 8.34, P = 0.039). In the childhood group there was an increased frequency of B8, DR3 and DQ2 compared with the adults which included five of 26 who were homozygous for these antigens, a feature not seen in the adults, which may account for the differences seen between the two groups. Possession of HLA B8, DR3 and DQ2 probably facilitates earlier presentation of the disease as there is no evidence from our results that the adults and children differ fundamentally in their MHC associations. The rare TNF2 allele was found in 29 of 51 patients (expected 8.2, chi2 = 18. 3, P = 0.0001). This was more marked in the children (19 of 26). Patients with the TNF2 allele had a longer disease duration (5.3 years TNF2, 3.0 years TNF1).

HLA class I and II typing of the patients with Behçet's disease in Saudi Arabia.

Thirteen Saudi Arabian patients with Behçet's disease (BD) were typed for HLA-A and -B alleles by the conventional serologic typing and for HLA-DRB1, -DQB1 and -DPB1 alleles by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. As a result, the phenotype frequency of the B51 antigen was significantly increased in the patient group as compared to the ethnically matched control group (76.9% in patients vs. 22.20% in controls), but no significant difference was observed in HLA-A, -DRB1, -DQB1 or -DPB1 alleles between the patients and controls, as previously observed in Japanese BD. Further, by HLA-B51 allelic genotyping performed by the polymerase chain reaction-sequence specific primers (PCR-SSP) method, all of the B51-positive patients and controls were found to carry one particular allele, B*5101, except one patient with B*5108.

Structure and chromosomal location of mouse and human CD52 genes

Human CD52 (CAMPATH-1 antigen) is an abundant surface molecule on lymphocytes and a favoured target for lymphoma therapy and immunosuppression. It comprises a small glycosylphosphatidylinositol (GPI) anchored peptide to which a large carbohydrate moiety is attached. Structurally similar proteins include the proposed mouse homologue, B7 antigen (B7-Ag; not to be confused with the CD28 ligand), and human and mouse CD24. Sequence similarities between CD52 and B7-Ag precursors are concentrated over the signal peptides and the sequences cleaved during GPI attachment. While the short mature peptides are not apparently homologous, the N-linked glycosylation site is retained in both. We describe similarities in exon–intron organisation, syntenic chromosome positions (human CD52, 1p36; mouse B7-Ag, chromosome 4, between Dsi1 and D4Nds16) and sequence homology in the promoter regions which strongly suggests that B7-Ag is the mouse homologue of CD52. The structure of these genes is also similar to that of mouse CD24, suggesting a common ancestor. Promoter activities and transcription start sites were also analysed. These results suggest that human CD52 and mouse B7-Ag gene expressions are controlled by TATA-less promoters.

Expression of B7 co-stimulatory molecules and CD1a antigen by alveolar macrophages in allergic bronchial asthma.

Lung allergen recognition that takes place in the airways of asthmatic subjects is still a controversial matter. We hypothesized that a rapid allergen recognition process requires the presence, at the mucosal surface, of professional APC, such as B7+ alveolar macrophages (AM) and/or CD1+ dendritic cells, which usually have a lower expression in the normal human lung. Studies were performed on bronchoalveolar lavage (BAL) fluid collected from 10 untreated allergic subjects and 10 adult normal volunteers. Further controls consisted of five untreated pulmonary sarcoidosis (PS) and four extrinsic allergic alveolitis (EAA) individuals. To ascertain whether T helper 2-type cytokines or allergen influence B7 and CD1 antigen expression, in vitro studies were carried out using unprimed (naive) cord blood plastic-adherent monocytes. Cytofluorymetric analysis revealed that AM from asthmatics, unlike those from normal subjects or patients with PS or EAA, overexpressed B7-2, CD1a and, to a lesser extent, B7-1 surface molecules. Immunohistochemical studies confirmed the presence of CD1+ dendritic cells in the BAL fluid from asthmatic subjects. On in vitro cultured naive cord blood monocytes both purified Dermatophagoides pteronyssinus allergen and T-cell cytokines, i.e. IL-4 and granulocyte macrophage colony-stimulating factor, induced surface expression of B7-2 and CD1a receptors, whereas they had no appreciable effect on that of B7-1 membrane molecule. Taken together, these findings support the proposal that airways of atopic individuals are equipped with professional APC that synergize with allergen-specific T cells for the recognition of intact allergens. When the recognition process takes place, asthmatic symptoms could develop in genetically susceptible individuals.

1 The spondylarthropathies: classification and diagnosis. Do we need new terminologies?

The present classification of a number of arthropathies linked to the B27 antigen under the term spondylarthropathy emphasises the frequent familial aggregation and clustering during follow-up of these diseases. This article is an attempt to review the progress elicited by the introduction of classification criteria for spondylarthropathy and the limitations of the concept. In particular, we address the continued need for better understanding of aetiology and pathogenesis. This makes it likely that we will need new classifications in the future and that this will evolve along with improvements in disease understanding. Working classifications that include the infectious triggers and features of the host response might be useful to guide new approaches.

RECURRENT EPIDIDYMO-ORCHITIS SECONDARY TO BEHCET'S DISEASE

No AccessJournal of UrologyClinical Urology: Case Reports1 Aug 1998RECURRENT EPIDIDYMO-ORCHITIS SECONDARY TO BEHCET'S DISEASE JOSE L. CALLEJAS-RUBIO, NORBERTO ORTEGO, ANTONIO DIEZ, MERCEDES CASTRO, and JOSE DE LA HIGUERA JOSE L. CALLEJAS-RUBIOJOSE L. CALLEJAS-RUBIO More articles by this author , NORBERTO ORTEGONORBERTO ORTEGO More articles by this author , ANTONIO DIEZANTONIO DIEZ More articles by this author , MERCEDES CASTROMERCEDES CASTRO More articles by this author , and JOSE DE LA HIGUERAJOSE DE LA HIGUERA More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)62936-7AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "RECURRENT EPIDIDYMO-ORCHITIS SECONDARY TO BEHCET'S DISEASE." The Journal of Urology, 160(2), p. 496 References 1 : Behcet's disease. Report of 41 cases and review of the literature. Medicine1975; 54: 179. Google Scholar 2 : Urological aspects of Behcet's disease. Brit. J. Urol.1991; 67: 638. Google Scholar 3 : Orchitis due to vasculitis in autoimmune diseases. Scand. J. Rheumatol.1997; 26: 151. Google Scholar Departments of Internal Medicine and Ophthalmology, San Cecilio University Hospital, Granada, Spain© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byCHO Y, JUNG J, LEE K, BANG D, LEE E and LEE S (2018) Clinical Features of Patients with Behçet's Disease and EpididymitisJournal of Urology, VOL. 170, NO. 4 Part 1, (1231-1233), Online publication date: 1-Oct-2003.KAKLAMANI V, VAIOPOULOS G, MARKOMICHELAKIS N and KAKLAMANIS P (2018) RECURRENT EPIDIDYMO-ORCHITIS IN PATIENTS WITH BEHÇET’S DISEASEJournal of Urology, VOL. 163, NO. 2, (487-489), Online publication date: 1-Feb-2000. Volume 160Issue 2August 1998Page: 496 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information JOSE L. CALLEJAS-RUBIO More articles by this author NORBERTO ORTEGO More articles by this author ANTONIO DIEZ More articles by this author MERCEDES CASTRO More articles by this author JOSE DE LA HIGUERA More articles by this author Expand All Advertisement PDF downloadLoading ...

Clinical manifestations of seronegative spondylarthropathies

Seronegative spondylarthropathies include ankylosing spondylitis, Reiter's syndrome and reactive arthritis, psoriatic arthritis, arthritis associated with ulcerative colitis and Crohn's disease, plus other forms which do not meet the criteria for definite categories and are called undifferentiated. Recently two sets of classification criteria have been proposed for the entire group including undifferentiated forms: the European Spondylarthropathy Study Group and the Amor criteria. The prevalence of spondylarthropathies is directly correlated with the prevalence of the HLA-B27 antigen in the population. The highest prevalence of ankylosing spondylitis (4.5%) has been found in Canadian Haida Indians, where 50% of the population is B27 positive. Among Europeans the frequency of the B27 antigen in the general population ranges from 3 to 13% and the prevalence of ankylosing spondylitis is estimated to be 0.1–0.23%. Seronegative spondylarthropathies have common clinical and radiologic manifestations: inflammatory spinal pain, sacroiliitis, chest wall pain, peripheral arthritis, peripheral enthesitis, dactylitis, lesions of the lung apices, conjunctivitis, uveitis and aortic incompetence together with conduction disturbances. All of these may also occur in isolation.

Behçet's disease and the nervous system.

Behçet's disease is a multisystem inflammatory disorder with unknown aetiology. It is a disease of young adults with a more severe course in males subjects. Its prevalence is high in the Mediterranean basin and Japan and has been linked with human leucocyte antigen B5 (HLA-B5) in those countries. According to the diagnostic criteria formed by the International Study Group, recurrent oral ulceration is a prerequisite, with two more typical symptoms or signs. Neurological involvement is one of the most devastating manifestations of Behçet's disease. The involvement is either caused by primary neural parenchymal lesions (neuro-Behçet) or secondary to major vascular involvement (vasculo Behçet). The course is relapsing-remitting, secondary progressive or primary progressive. The most commonly involved area is the brain stem, with additional symptoms or signs, hemispherical involvement with mental changes being the most common. Intracranial hypertension, usually owing to dural sinus thrombosis, has a special place in Behçet's disease. The most common clinical findings are pyramidal signs. Sensory symptoms or signs are much less frequent, and hemianopia and higher cortical function disturbances as well as pure cerebellar syndrome are rare features. Cerebrospinal fluid usually has a high protein content and/or pleocytosis. Notably, in the acute period most patients have lesions shown by magnetic resonance imaging (MRI) extending from the brain-stem to diencephalic structures. Differential diagnosis from multiple sclerosis can be difficult in patients with hemispheric white matter MRI hyperintensities. Immunosuppressives are used in treatment.

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis.

The present study is an analysis of the frequencies of HFE mutations in patients with different forms of iron overload compared with the frequencies found in healthy subjects from the same region. The frequencies of HLA-A and -B antigens and HLA haplotypes were also analyzed in the same subjects. The study population included: 71 healthy individuals; 39 genetically and clinically well-characterized patients with genetic hemochromatosis (HH); and 25 patients with non-classical forms of iron overload (NCH), excluding secondary hemochromatosis. All subjects were HLA-typed and HFE-genotyped by the oligonucleotide ligation assay (OLA). The gene frequencies found for the C282Y and H63D mutations of HFE were respectively: 0.03 and 0.23 in healthy individuals, 0.86 and 0.04 in HH patients, and 0.08 and 0.48 in NCH patients. An expected significant association between HH and HLA-A3 was observed, which was found to be in linkage disequilibrium with the C282Y mutation. A new association was seen, however, between HLA-A29 and NCH, in linkage disequilibrium with the H63D mutation. Again as expected, the HLA-B antigen B7 was associated with HH in linkage disequilibrium with HLA-A3. In addition, the HLA-B antigen B44 was found to be associated with NCH but not in linkage disequilibrium with either A29 or the H63D mutation. In conclusion, a new association of the HFE H63D mutation with forms of hemochromatosis other than HH and a new association between the HLA phenotype A29 and the HFE H63D mutation were found in the same patients. These findings reinforce evidence for the involvement of the major histocompatibility class I in iron metabolism, supporting the notion of a physiological role for the immunological system in the regulation of iron load.