British Journal of Rheumatology 1992;31:771-772 SPECIAL INTEREST GROUP REPORT
SERONEGATIVE ARTHRITIS BY R. HUGHES Rheumatology Department, Westminster Hospital, 17 Page Street, London SW1P 2AP
pectively assess 10 patients with AS using a composite index score incorporating a variety of laboratory measures (CRP, immunoglobulins and serum saved for measurement of anti-microbial antibody), VAS assessing pain and stiffness and a functional index modified from an 'Oswestry assessment scale' to be completed by the patients themselves. By the time of the next Special Interest Group meeting in Harrogate in 1993 results from this small scale exercise should be available for further discussion. One of the factors that most inhibits progress in developing indices such as these, or indeed in performing any piece of clinical research involving relatively uncommon rheumatic diseases is the availability, sometimes at short notice, of adequate numbers of well-documented patients and suitable samples of blood, synovial fluid and synovium. It emerged that many of those at this meeting had experienced this problem. Dr Andrew Keat suggested that this Special Interest Group might initiate the establishment of a central 'library' of samples and computer-stored clinical information to be collected nationally from patients with rheumatic disease to be readily accessible to those undertaking approved research projects. Such a bank of material might help to accelerate the pace of future research into seronegative arthritis and rheumatic disease in general. Dr Keat agreed, on behalf of the group, to sketch out a preliminary plan in the form of a grant application seeking funding for the establishment of a computer data base and to allow for the collection and storage of samples. The key to the success of this project would be the appointment of a 'facilitator' to co-ordinate documentation, collection and storage of material. Funding would be necessary to pay the salary to employ such a person. A preliminary document should be available for discussion prior to the next meeting at which a steering committee might be established. As an added bonus for attendance we were then introduced to two new areas of research work by Dr Jim Archer (Royal London Hospital). Endothelial cell stimulating angiogenic factor (ESAF), he told those of us not 'in the know', is a substance of low molecular mass which activates TIMP-inhibited collagenase [1]. It is probably found in high levels at bone growth plates where new blood vessel formation is accompanied by calcification. Preliminary studies by Jackie Weiss (Manchester) suggest that ESAF levels in serum may vary with activity of AS as judged by an enthesis index. ESAF, therefore, may be a marker of disease activity in
0263-7103/92/011711 + 02 $08.00/0
© 1992 British Society for Rheumatology 771
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Sussex on August 23, 2015
IT was encouraging that several clear objectives emerged from the Special Interest Group meeting on Seronegative Arthritis, held on the afternoon of the first day of the Spring British Society for Rheumatology meeting in Southampton. The chairman on this occasion, Dr Andrew Keat (Westminster), invited Professor Roger Sturrock (Glasgow) to open the discussion with an update on progress towards the development of a disease activity index for the assessment of patients with ankylosing spondylitis (AS). An effective index should, it was generally agreed, reflect overall disease severity as well as being of help in quantifying any effect that might result from drug treatment. Professor Sturrock presented a preliminary, uncontrolled study from his unit in Glasgow, comparing the use of a new 'Glasgow Enthesis Index' (El) with the Glasgow Activity Index (AI), a composite scale measuring erythrocyte sedimentation rate, C-reactive protein (CRP), immunoglobulin levels, peripheral joint count, visual analogue scale (VAS) of pain and stiffness and the degree of non-steroidal anti-inflammatory drugs use by the patient. The new El is similar to the Ritchie Index and quantifies a patients' subjective response to mechanical pressure, in this case over a defined number of entheses. Not surprisingly, the only correlation between the two scales was found when the El was compared with the VAS component of the Activity Index. All other correlation was poor. It may be necessary, it was concluded, to measure many variables in order to get a comprehensive picture of disease activity in AS. With a brief show of territorial behaviour several points were made. In decrying laboratory measures of AS activity as being of no help in assessing patients with spinal disease but no involvement of peripheral joints, Dr Andrei Calin (Bath) proposed that VAS measures alone would be effective. Dr Alan Ebringer (Middlesex and University College Hospital), on the other hand, supported the use of laboratory variables and particularly the serial measurement of serum antibody directed against specific bacterial antigens such as Klebsiella. Dr Andrew Frank (Northwick Park) spoke from the rehabilitation corner. He maintained that no measure of AS activity was complete without some measure of any functional disability experienced by patients with spinal disease. It was finally agreed that a member of each Rheumatology Unit represented at the meeting should prosAccepted 29 July 1992. Correspondence to R. Hughes.
772
BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. 11 is present in all its subtypes. Cytokines that are produced in the joint in response to the presence of microbial antigens could initiate a reaction against the 'wrong' peptides presented on HLA B27 giving one possible mechanism by which excessive inflammatory response might occur. Further work is under way [2]. REFERENCES
1. Jones PB, Fakhoury RJ, Weiss JB. Increased levels of angiogenesis factor activity correlate with inflammatory index in ankylosing spondylitis. Br J Rheumatol 1992;31(Suppl.2):12. 2. Maclean L, Macey M, Lowdell M, Badakere S, Whelan, Perrett D, Archer J. Sulphydryl reactivity of the HLA-B27 epitope: accessibility of the free cysteine studied by flow cytometry. Ann Rheum Dis 1992;51:456-60.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Sussex on August 23, 2015
AS. All the more reason for having serum samples readily available from a large number of patients with AS to test such an hypothesis. The second new area of research involved the chemical complexities of the HLA B27 molecule. At position 67 in the antigen binding groove of the HLA B27 protein lies a cysteine residue (CYS67), with a sulphydryl side-chain (-SH) that can provide a target for oxidation. Alongside CYS67 in the molecular configuration of HLA B27, at position 70, is a lysine with an exposed amino side-chain (-NHj) that, under certain conditions, associates with the neighbouring cysteine to increase its chemical reactivity. Dr Archer proposes that chemical changes in CYS67 alter the specificity of HLA B27 for peptides so that it confuses the T cell by presenting the wrong antigen. Moreover, the cysteinelysine relationship seems to be unique to HLA B27 and
SERONEGATIVE ARTHRITIS BY R. HUGHES Rheumatology Department, Westminster Hospital, 17 Page Street, London SW1P 2AP
pectively assess 10 patients with AS using a composite index score incorporating a variety of laboratory measures (CRP, immunoglobulins and serum saved for measurement of anti-microbial antibody), VAS assessing pain and stiffness and a functional index modified from an 'Oswestry assessment scale' to be completed by the patients themselves. By the time of the next Special Interest Group meeting in Harrogate in 1993 results from this small scale exercise should be available for further discussion. One of the factors that most inhibits progress in developing indices such as these, or indeed in performing any piece of clinical research involving relatively uncommon rheumatic diseases is the availability, sometimes at short notice, of adequate numbers of well-documented patients and suitable samples of blood, synovial fluid and synovium. It emerged that many of those at this meeting had experienced this problem. Dr Andrew Keat suggested that this Special Interest Group might initiate the establishment of a central 'library' of samples and computer-stored clinical information to be collected nationally from patients with rheumatic disease to be readily accessible to those undertaking approved research projects. Such a bank of material might help to accelerate the pace of future research into seronegative arthritis and rheumatic disease in general. Dr Keat agreed, on behalf of the group, to sketch out a preliminary plan in the form of a grant application seeking funding for the establishment of a computer data base and to allow for the collection and storage of samples. The key to the success of this project would be the appointment of a 'facilitator' to co-ordinate documentation, collection and storage of material. Funding would be necessary to pay the salary to employ such a person. A preliminary document should be available for discussion prior to the next meeting at which a steering committee might be established. As an added bonus for attendance we were then introduced to two new areas of research work by Dr Jim Archer (Royal London Hospital). Endothelial cell stimulating angiogenic factor (ESAF), he told those of us not 'in the know', is a substance of low molecular mass which activates TIMP-inhibited collagenase [1]. It is probably found in high levels at bone growth plates where new blood vessel formation is accompanied by calcification. Preliminary studies by Jackie Weiss (Manchester) suggest that ESAF levels in serum may vary with activity of AS as judged by an enthesis index. ESAF, therefore, may be a marker of disease activity in
0263-7103/92/011711 + 02 $08.00/0
© 1992 British Society for Rheumatology 771
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Sussex on August 23, 2015
IT was encouraging that several clear objectives emerged from the Special Interest Group meeting on Seronegative Arthritis, held on the afternoon of the first day of the Spring British Society for Rheumatology meeting in Southampton. The chairman on this occasion, Dr Andrew Keat (Westminster), invited Professor Roger Sturrock (Glasgow) to open the discussion with an update on progress towards the development of a disease activity index for the assessment of patients with ankylosing spondylitis (AS). An effective index should, it was generally agreed, reflect overall disease severity as well as being of help in quantifying any effect that might result from drug treatment. Professor Sturrock presented a preliminary, uncontrolled study from his unit in Glasgow, comparing the use of a new 'Glasgow Enthesis Index' (El) with the Glasgow Activity Index (AI), a composite scale measuring erythrocyte sedimentation rate, C-reactive protein (CRP), immunoglobulin levels, peripheral joint count, visual analogue scale (VAS) of pain and stiffness and the degree of non-steroidal anti-inflammatory drugs use by the patient. The new El is similar to the Ritchie Index and quantifies a patients' subjective response to mechanical pressure, in this case over a defined number of entheses. Not surprisingly, the only correlation between the two scales was found when the El was compared with the VAS component of the Activity Index. All other correlation was poor. It may be necessary, it was concluded, to measure many variables in order to get a comprehensive picture of disease activity in AS. With a brief show of territorial behaviour several points were made. In decrying laboratory measures of AS activity as being of no help in assessing patients with spinal disease but no involvement of peripheral joints, Dr Andrei Calin (Bath) proposed that VAS measures alone would be effective. Dr Alan Ebringer (Middlesex and University College Hospital), on the other hand, supported the use of laboratory variables and particularly the serial measurement of serum antibody directed against specific bacterial antigens such as Klebsiella. Dr Andrew Frank (Northwick Park) spoke from the rehabilitation corner. He maintained that no measure of AS activity was complete without some measure of any functional disability experienced by patients with spinal disease. It was finally agreed that a member of each Rheumatology Unit represented at the meeting should prosAccepted 29 July 1992. Correspondence to R. Hughes.
772
BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. 11 is present in all its subtypes. Cytokines that are produced in the joint in response to the presence of microbial antigens could initiate a reaction against the 'wrong' peptides presented on HLA B27 giving one possible mechanism by which excessive inflammatory response might occur. Further work is under way [2]. REFERENCES
1. Jones PB, Fakhoury RJ, Weiss JB. Increased levels of angiogenesis factor activity correlate with inflammatory index in ankylosing spondylitis. Br J Rheumatol 1992;31(Suppl.2):12. 2. Maclean L, Macey M, Lowdell M, Badakere S, Whelan, Perrett D, Archer J. Sulphydryl reactivity of the HLA-B27 epitope: accessibility of the free cysteine studied by flow cytometry. Ann Rheum Dis 1992;51:456-60.
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Sussex on August 23, 2015
AS. All the more reason for having serum samples readily available from a large number of patients with AS to test such an hypothesis. The second new area of research involved the chemical complexities of the HLA B27 molecule. At position 67 in the antigen binding groove of the HLA B27 protein lies a cysteine residue (CYS67), with a sulphydryl side-chain (-SH) that can provide a target for oxidation. Alongside CYS67 in the molecular configuration of HLA B27, at position 70, is a lysine with an exposed amino side-chain (-NHj) that, under certain conditions, associates with the neighbouring cysteine to increase its chemical reactivity. Dr Archer proposes that chemical changes in CYS67 alter the specificity of HLA B27 for peptides so that it confuses the T cell by presenting the wrong antigen. Moreover, the cysteinelysine relationship seems to be unique to HLA B27 and
