Objective: Hand and upper limb involvement is common in patients with rheumatoid arthritis ( RA). However, its impact on manual activities of daily life has not been fully evaluated. A measure of manual ability was developed, through the Rasch measurement model, by adapting and validating the ABILHAND questionnaire, which measures the patient's perceived difficulty in performing everyday manual activities.Methods: 112 patients with RA were evaluated. The following tests were performed: the ABILHAND questionnaire, the Health Assessment Questionnaire (HAQ), the Jamar grip and key pinch strength tests, the Box and Block dexterity test and the Purdue pegboard dexterity test. In total, 35 patients were reassessed to determine the test - retest reliability of the ABILHAND, and 6 patients were studied before and after therapy with tumour necrosis factor (TNF) blockers to address sensitivity to change.Results: The Rasch refinement of the ABILHAND led to a selection of 27 items rated on a 3-point scale. The resulting ability scale was targeted to the ability of the patients. The item- difficulty hierarchy was stable across demographic and clinical subgroups and over time. Grip and key pinch strength and manual and digital dexterity on both hands were significantly, though moderately, correlated with the ABILHAND measures. Manual ability was also significantly related to the number of affected hands, disease duration, tender and swollen joint counts on upper limbs, disease activity and the HAQ. Sensitivity to change was demonstrated in patients treated with TNF blockers, commensurate with their clinical improvement.Conclusion: The ABILHAND questionnaire is a clinically valid person- centred measure of manual ability that could be useful in longitudinal RA studies.

We have identified a gene encoding an antigen recognized by cytolytic T lymphocytes on the autologous tumor cells of a melanoma patient, AVL3. The gene shows homologies with members of the HERV-K family of human endogenous retroviruses, and it was provisionally named HERV-K-MEL. It contains many mutations that disrupt the open reading frames coding for all of the viral proteins. The HERV-K-MEL gene is not expressed in normal tissues with the exception of testis and some skin samples. It is expressed in most samples of cutaneous and ocular melanoma. It is also expressed in a majority of naevi and in a minority of carcinomas and sarcomas. The antigenic peptide, presented by HLA-A2 molecules, is encoded by a very short open reading frame present in the env region of a spliced HERV-K-MEL transcript. Anti-HERV.A2 CTLp could not be detected in the blood of three individuals without cancer but were present at a frequency of 3 x 10(-5) among blood CD8 T cells in patient AVL3 and 6 x 10(-7) in another HLA-A2 melanoma patient whose tumor expressed HERV-K-MEL. Anti-HERV.A2 CTL clones derived from each patient lysed melanoma cells. Analysis of T-cell receptor beta chain sequences indicated that the anti-HERV.A2 CTL population was oligoclonal in patient AVL3 and probably monoclonal in the other patient. These results suggest that HERV-K-MEL is a source of antigens that are targeted by CTLs in melanoma patients and could therefore be used for vaccination.

We have identified an antigen recognized by autologous CTL on the lung carcinoma cells of a patient who enjoyed a favorable clinical evolution, being alive 10 years after partial resection of the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and encoded by a mutated sequence in the gene coding for malic enzyme, an essential enzyme that converts malate to pyruvate. In the tumor cell line derived from the patient, only the mutated malic enzyme allele is expressed, because of a loss of heterozygosity in the region of chromosome 6 that contains this locus. Tetramers of soluble HLA-A2 molecules loaded with the antigenic peptide stained approximately 0.4% of the patient's blood CD8 T cells. When these cells were stimulated in clonal conditions, 25% of them proliferated, and the resulting clones were lytic and specific for the mutated malic enzyme peptide. T-cell receptor analysis indicated that almost all of these antimalic CTLs shared the same receptor. Antimalic T cells were consistently found in blood samples collected from the patient between 1990 and 1999, at frequencies ranging from 0.1 to 0.4% of the CD8 cells. Their frequency appeared to double within 2 weeks after intradermal inoculation of lethally irradiated autologous tumor cells. These results indicate that nonmelanoma cancer patients may also have a high frequency of blood CTLs directed against a tumor-specific antigen.

We derived lung carcinoma cell lines from tumor material resected from a patient with small-cell lung cancer (SCLC) and from a patient with non-small-cell lung cancer (NSCLC). The patient with NSCLC was vaccinated with irradiated autologous tumor cells. The two patients enjoyed an exceptionally favorable clinical evolution and are currently without signs of cancer 10 and 8 yr after their diagnoses, respectively. Autologous mixed lymphocyte-tumor cell cultures (MLTC) were produced with blood lymphocytes stimulated with irradiated autologous tumor cells. The first patient's SCLC cells, which carried a small amount of human leukocyte antigen (HLA) class I molecules, were incubated with interferon-gamma (IFN-gamma) before being used as stimulator cells. A cytolytic T-lymphocyte (CTL) clone was derived that specifically lysed the IFN-gamma-treated SCLC cells but did not lyse untreated tumor cells or autologous lymphoblasts. Clones of autologous tumor-specific CTL, directed against the NSCLC cells of the other patient, were also obtained. These tumor cells carried a higher level of HLA class I molecules and were lysed by the CTL without incubation with IFN-gamma. Altogether, these results indicate that SCLC and NSCLC cancer cells can be recognized by autologous CTL, and might therefore be susceptible to specific immunotherapy.

We have pursued our analysis of antigens recognized by autologous cytolytic T lymphocytes (CTLs) on the melanoma cells of patient LB33. This patient enjoys an unusually favorable evolution, which is associated with a strong and sustained antitumor CTL response. We reported previously the analysis of two melanoma cell lines, MEL.A and MEL.B, which were derived from metastases removed from the patient at 5 years’ distance. Autologous CTL clones derived from blood lymphocytes recognized several antigens presented by different HLA class I molecules on MEL.A. The MEL.B cells resisted lysis by these CTLs because they have lost expression of most HLA molecules, suggesting that they were selected in vivo by the anti-MEL.A CTL response. One of the MEL.A antigens was shown to result from a point mutation in the tumor. Here we report the cloning of a gene that encodes two other MEL.A antigens. This new gene, MUM-2, is expressed ubiquitously. In the melanoma cells of patient LB33, it contains a point mutation that changes one amino acid in the translated protein. Two different antigenic peptides, one presented to CTL by HLAB44 molecules and another by HLA-C6 molecules, overlap and contain the mutated residue. GeneMUM-2 is homologous to an essential yeast gene, bet5, that was recently shown to be implicated in the vesicular transport of proteins from the endoplasmic reticulum to the Golgi. In a mutant yeast with a disrupted bet5gene, both the wild-type and the mutatedMUM-2 genes could complement forbet5function. These results indicate that the antigenic mutation does not destroy the function of the protein, a function that is conserved in eukaryotic cells. The identification of these antigens suggests that point mutations could be the major cause of the strong immunogenicity of MEL.A cells.

Tissue AntigensVolume 49, Issue 3 p. 274-276 A new silent mutation at codon 35 in exon 2 yielding DRB1*04012 allele J. Thonnard, Corresponding Author J. Thonnard Laboratory of Clinical Molecular BiologyClinical Molecular Biology, UCL 3046 University Hospital of St-Luc Clos chapelle aux champs, 30 B-1200 Brussels Belgium Fax +32 2 764 39 59 E-mail thonnard@gece.ucl.ac.beSearch for more papers by this authorT. Gervais, T. Gervais Immunohematology Laboratory, Hospital St Luc, Catholic University of Louvain, Brussels, BelgiumSearch for more papers by this authorM. Heusterspreute, M. Heusterspreute Laboratory of Clinical Molecular BiologySearch for more papers by this authorG. Mersch, G. Mersch Innogenetics N. V., Ghent, BelgiumSearch for more papers by this authorI. De Canck, I. De Canck Innogenetics N. V., Ghent, BelgiumSearch for more papers by this authorC. De Greet, C. De Greet Histocompatibility Laboratory, Academic Brussels Hospital Free University (AZ-VUB), Brussels, BelgiumSearch for more papers by this authorC. Demanet, C. Demanet Histocompatibility Laboratory, Academic Brussels Hospital Free University (AZ-VUB), Brussels, BelgiumSearch for more papers by this authorC. Van Waeyenberge, C. Van Waeyenberge Histocompatibility Laboratory, Academic Brussels Hospital Free University (AZ-VUB), Brussels, BelgiumSearch for more papers by this author J. Thonnard, Corresponding Author J. Thonnard Laboratory of Clinical Molecular BiologyClinical Molecular Biology, UCL 3046 University Hospital of St-Luc Clos chapelle aux champs, 30 B-1200 Brussels Belgium Fax +32 2 764 39 59 E-mail thonnard@gece.ucl.ac.beSearch for more papers by this authorT. Gervais, T. Gervais Immunohematology Laboratory, Hospital St Luc, Catholic University of Louvain, Brussels, BelgiumSearch for more papers by this authorM. Heusterspreute, M. Heusterspreute Laboratory of Clinical Molecular BiologySearch for more papers by this authorG. Mersch, G. Mersch Innogenetics N. V., Ghent, BelgiumSearch for more papers by this authorI. De Canck, I. De Canck Innogenetics N. V., Ghent, BelgiumSearch for more papers by this authorC. De Greet, C. De Greet Histocompatibility Laboratory, Academic Brussels Hospital Free University (AZ-VUB), Brussels, BelgiumSearch for more papers by this authorC. Demanet, C. Demanet Histocompatibility Laboratory, Academic Brussels Hospital Free University (AZ-VUB), Brussels, BelgiumSearch for more papers by this authorC. Van Waeyenberge, C. Van Waeyenberge Histocompatibility Laboratory, Academic Brussels Hospital Free University (AZ-VUB), Brussels, BelgiumSearch for more papers by this author First published: 11 December 2008 https://doi.org/10.1111/j.1399-0039.1997.tb02751.xCitations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume49, Issue3March 1997Pages 274-276 RelatedInformation

To investigate the association between genes in the major histocompatibility complex and inner ear disease susceptibility at the DNA level, high-resolution genotyping for HLA class II (HLA-DR, -DQ, -DP) was performed by polymerase chain reaction-sequence specificoligonucleotide reverse dot blot and polymerase chain reaction-restriction fragment length polymorphism analysis in 34 patients with idiopathic progressive sensorineural hearing loss (PSHL) and in 214 controls. The frequencies of DRB1*0301, DRB3*0101, DQB1*0201, and DPB1*0401 were significantly increased in patients with idiopathic PSHL compared with controls. The DQB1*0301 allele was significantly decreased in the patients. A linkage disequilibrium was probably responsible for the concomitant increase of both DRB1*0301 and DRB3*0101 alleles in patients. The increase of DQB1*0201 in patients was associated with the DRB1*0301 allele. In addition, the telomeric DPB1*0401 allele may act as an independent risk factor. The DQB1*0301 allele may have a protective role in the pathogenesis of idiopathic PSHL. These results suggest that the specific HLA class II gene products may confer susceptibility or resistance to idiopathic PSHL.

The molecular basis of beta-thalassemia was investigated at the DNA level in 28 Belgians from 14 unrelated families. All the patients were heterozygous for beta-thalassaemia. Seven different mutations were identified using a combination of dot-blot hybridization with allele-specific oligonucleotide probes and direct automated fluorescence-based DNA sequencing. Among these mutations, four are commonly found in the Mediterraneans - codon 8 (-AA), IVS-I-1 (G --> A), IVS-I-6 (T --> C) and codon 39 (C --> T)-and two have occasionally been reported-initiation codon (T --> C) and codon 35 (C --> A). The last mutation, a -CC deletion at codons 38/39, appears to be a novel mutation and can routinely be investigated by AvaII restriction on amplified DNA. We report our findings, discuss the diversity of the mutations found in Belgium and show the usefulness of direct DNA sequencing in a population in which the molecular defects of beta-thalassaemia have yet to be characterized and in which screening is hampered by the wide range of potential mutations.

Tissue AntigensVolume 46, Issue 2 p. 124-127 A new HLA-DRB1*1116 allele sharing DR13 and DR11 sequence motifs J. Thonnard, Corresponding Author J. Thonnard Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, Belgium**Clinical Laboratory of Molecular Biology University Medical School of Louvain Clos Chapelle-aux-champs UCL 3046 B-1200 Brussels, BelgiumSearch for more papers by this authorB. Blaimond, B. Blaimond Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this authorM. Heusterspreut, M. Heusterspreut Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this authorN. Straetmans, N. Straetmans Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this authorM. Philippe, M. Philippe Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this author J. Thonnard, Corresponding Author J. Thonnard Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, Belgium**Clinical Laboratory of Molecular Biology University Medical School of Louvain Clos Chapelle-aux-champs UCL 3046 B-1200 Brussels, BelgiumSearch for more papers by this authorB. Blaimond, B. Blaimond Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this authorM. Heusterspreut, M. Heusterspreut Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this authorN. Straetmans, N. Straetmans Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this authorM. Philippe, M. Philippe Clinical Laboratory of Molecular Biology, University Medical School of Louvain, Brussels, BelgiumSearch for more papers by this author First published: August 1995 https://doi.org/10.1111/j.1399-0039.1995.tb02488.xCitations: 12AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Bidwell J. Advances in DNA-based HLA-typing methods. Immunol Today 1994; 15: 303–307. 2 Bodmer JG, March SGE, Albert ED et al. Nomenclature for factor of HLA system, 1994. Tissue Antigens 1994; 44: 1–18. 3 Buyse I, Decorte R, Baens M et al. Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridization. Tissue Antigens 1993; 41: 1–14. 4 Ota M, Seki T, Fukushima H, Tsuji K, Inoko H. HLA-DRB1 genotyping by modified PCR-RFLP method combined with group-specific primers. Tissue Antigens 1992; 39: 187–202. 5 Sengar PDS, Goldstein R, Toye B, Hampton N. Comprehensive typing of DR52(DRB3)-associated DRB1 and DRB3 alleles by PCR-RFLP. Tissue Antigens 1994; 43: 295–301. 6 Smith AG, Safirman C, Kelso C, Amar A, Hansen JA, Brautbar C. Two new DR52-associated alleles DRB1*1111 and 1312, identified by PCR/SSOP and confirmed by DNA sequencing. Tissue Antigens 1994; 44: 52–56. 7 Laforet M, Urlacher A, Falkenrodt A, Liourne B, Parassiadis A, Tongio MM. A new allele (DRB1*1411) containing a short DR11 sequence and its haplotypic association. Hum Immunol 1993; 36: 179–185. 8 Tiercy JM, Gebuher L, Betuel H, Mach B, Jeannet M. A new HLA-DR4 allele with a DR11 alpha-helix sequence. Tissue Antigens 1993; 41: 97–101. 9 Brown JH, Jardetzky TS, Gorga JC et al. Three-dimentional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993; 364: 33–39. 10 Stern LJ, Brown JH, Jardetzky TS et al. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 1994; 368: 215–221. Citing Literature Volume46, Issue2August 1995Pages 124-127 ReferencesRelatedInformation

In the last few years, a variety of DNA-based human leukocyte antigen (HLA) typing methods have emerged, revealing the extreme polymorphism of HLA genes. This polymorphism makes it difficult for a clinical laboratory to establish the best HLA typing strategy. In this study we have compared two techniques for performing HLA-DRB typing: a commercial rapid assay based on the polymerase chain reaction (PCR) followed by reverse dot-blot hybridization of the PCR products (the Inno-LiPA assay), and a method based on PCR followed by restriction fragment length polymorphism analysis. We found that both methods provide reliable results with a high rate of concordance (97%) and that Inno-LiPA is convenient for large-scale routine typing. However, if a high-resolution allelic typing is required, each method lacks accuracy but using them in association improves the accuracy of the results.

SummarySeveral years ago, Rochalimaea henselae has emerged as an agent of bacillary angiomatosis, bacillary peliosis and recurrent septicaemia that generally occur in patients infected with human immunodeficiency virus. An aetiologic role in cat scratch disease is also suspected widely on the basis of a serologic survey. Its slow growth and its culture requirement explain that this pathogen, a gram-negative bacterium, could not be isolated until 1990. Moreover, blood and tissue samples request lysis and crushing for recovering by culture. The clinical, histological, microbiological and pathogenic aspects of these in; fcctions are described and discussed.

Several years ago, Rochalimaea henselae has emerged as an agent of bacillary angiomatosis, bacillary peliosis and recurrent septicaemia that generally occur in patients infected with human immunodeficiency virus. An aetiologic role in cat scratch disease is also suspected widely on the basis of a serologic survey. Its slow growth and its culture requirement explain that this pathogen, a gram-negative bacterium, could not be isolated until 1990. Moreover, blood and tissue samples request lysis and crushing for recovering by culture. The clinical, histological, microbiological and pathogenic aspects of these infections are described and discussed.