Abstract
The 5th Asian Congress on Autoimmunity took place in Suntec City, Singapore, on the 17–19 November 2011 under the presidency of Yehuda Shoenfeld (Chaim Sheba Medical Center, Ramat Gan, Israel). Senior investigators from a range of fields – including immunology, autoimmunity, rheumatology, neurology and hepatology – attended the conference. The scientific program placed an emphasis on the pathogenesis, genetic basis and mechanistic aspects of autoimmune diseases, as well as their clinical outcomes and treatment options. Particular focus was placed on systemic lupus erythematosus, rheumatoid arthritis, Type I diabetes, antiphospholipid syndrome and autoimmune hepatitis. Participants from over 50 countries attended the conference.
The last Asian Congress on Autoimmunity was recently held in Singapore (17–19 November 2011). This congress focused on the pathogenesis, genetics, mechanisms and clinical aspects of autoimmune diseases and their treatment modalities. Clinicians, immunologists, rheumatologists and experts in other fields of medicine involved in the diagnosis, treatment and research of autoimmune diseases gathered in the same place at the same time. Furthermore, hepatologists, engineers and many other professionals participated in this year’s congress. The congress was held in the historic Suntec City International Convention and Exhibition Center, Singapore, with over 300 participants. Participants came from many countries in Asia as well as from other parts of the world, such as France, Sweden, Spain, the UK and Australia. Yehuda Shoenfeld (Chaim Sheba Medical Center, Ramat Gan, Israel) was the honorary President of this congress. Pao-Hsii Feng (Raffles Hospital, Singapore) and Kok-Yong Fong (Singapore General Hospital, Singapore) were appointed as Co-Chairmen of the local organizing committee. Members were senior physicians from China, Korea, Japan and India.
There were two plenary sessions, ten parallel sessions and two free communication sessions focused on diagnosis and pathogenesis, immune regulation, autoimmunity and associated conditions, and experimental therapies. The free communication sessions and parallel sessions were run at two different halls.
Furthermore, three industry-supported, theme-based symposia were organized that focused on the ‘treat-to-target’ of rheumatoid arthritis (RA) and clinical utility of ultrasound in the diagnosis and prognosis of RA, which also focused on the basic science of animal models. The participants each received a copy of the text book ‘Diagnostic Criteria in Autoimmune Diseases’ signed personally by Shoenfeld Citation[1].
17 November 2011
The congress was started with a satellite symposium entitled ‘Antibodies’ chaired by Shoenfeld and Tom Williamson (Bio-Rad Laboratories, CA, USA). The session opened with an introduction and opening remarks by Shoenfeld, and it included a lecture entitled ‘Laboratory testing could be hazardous for your health – a look at test utilization for autoantibody testing’ by Michael Astion (University of Washington, DC, USA). He presented the current status on the understanding of autoantibodies and highlighted doctors’ misunderstandings. Thomas S Alexander (Summa Health System, OH, USA) presented autoantibody case studies. He explained positive predictive values and the pretest value of several tests in the clinical field.
The plenary sessions were chaired by Pao-Hsii Feng and Kok-Yong Fon and included a plenary lecture on ‘Micromanagement of lupus autoimmunity by microRNAs’ by Shen Nan (Shanghai Jiao Tong University, Shanghai, China). Shen Nan first reviewed miRNAs, which have recently been identified as regulators that modulate target gene expression and are necessary in the immune response. He assessed the profiling of miRNAs in systemic lupus erythematosus patients. He focused on the expression of miR-146a, which suppresses innate immunity. The expression of miR-146a was found to be correlated with clinical disease activity in patients with systemic lupus erythematosus.
The first day of congress was ended with an opening session on ‘The ASIA syndrome (Autoimmunity Syndromes Induced by Adjuvants)’ by Shoenfeld. He discussed HBV-related vasculitis after hepatitis B vaccination. He explained that even complete Freund’s adjuvant could induce systemic autoimmune syndrome in mice.
18 November 2011
The second day of the congress started with the plenary session on autoimmunity and associated conditions chaired by Tatuya Atsumi (Hokkaido University, Sapporo, Japan) and Yujiro Kon (Hokkaido University) entitled ‘Diagnostics’. The former lecture presented various antiprothrombin antibodies, such as antibodies that bind to prothrombin coated on γ-irradiated or activated polyvinyl chloride ELISA plates (antiprothrombin antibody [aPT]), or prothrombin exposed to immobilized phosphatidylserine (phospatidylserine-dependent antiprothrombin antibodies [aPS/PT]). No association between aPT and the risk of thrombosis was found. By contrast, the aPS/PT strongly correlate with the presence of lupus anticoagulant, and both sensitivity and specificity of aPS/PT for the diagnosis of antiphosphoslipid syndrome (APS) were demonstrated to be higher than those for aPT. Takao Koike (Hokkaido University) further investigated the predictive value of aPS/PT in their autoimmune cohort of the patients. Patients with IgG aPS/PT had a stronger risk of thrombosis than those without (odds ratio: 5.74; 95% CI: 2.2–14.7). The positive predictive values for IgG aPS/PT were higher than those of other antiphospholipid antibodies tested. He concluded that IgG aPS/PT was a useful predictive marker of thrombosis in patients with autoimmune diseases.
After a coffee break, two sponsored symposia were held and chaired by Koike, Feng and Hitoshi Kohsaka (Tokyo Medical and Dental University, Tokyo, Japan), titled ‘The next stage of RA management: evidence evolved from Asia’. The current status and future perspective of RA treatment in Japan was discussed in this session. Hisashi Yamanaka (Tokyo Women’s Medical University, Tokyo, Japan) presented on improved management of patients with RA by the introduction of new drugs and new therapeutic strategies. The remarkable changes in the disease activity, disability and remission rate were clearly demonstrated in their observational cohort, IORRA, which has been conducted in their university from 2000. From 2000 to 2010, patients in remission increased from 8 to 33% by the conventional disease activity score in 28 joints (DAS28) criteria, whereas patients from the new American College of Rheumatology/the European League Against Rheumatism Boolean practice criteria increased from 5 to 25%. Half of the patients were still in moderate disease activity. Recently, the target of RA therapy has been changed to treat until complete remission. He suggested that the use of methotrexate in a sufficient dose and the early introduction of biologics would achieve this idea.
After this, Tsutomu Takeuchi (Keio University, Tokyo, Japan) presented ‘New treatment strategy for individual RA patients by ‘treat-to-target’’ – he explained the RISING study, which was a multicenter, randomized, double-blind study conducted in Japan that proved the efficacy of 10 mg/kg to be higher than that of 3 mg/kg of infliximab, and the lowest serum trough level for obtaining clinical efficacy to be 1 µg/ml. This led to the approval of dose optimization of up to 10 mg/kg and the shortening of infusion intervals by up to 4 weeks. If it were possible to determine the necessary dose of infliximab before starting treatment, it would enable us to obtain a tighter control of disease activity and an earlier attainment of clinical remission. Therefore, Takeuchi’s group did a subanalysis of the RISING study on the efficacy of infliximab, according to the baseline plasma TNF-α levels. As a result, patients for whom baseline TNF-α levels were high had significantly higher clinical efficacy when the infliximab dose was higher. On the contrary, in patients with low baseline TNF-α, high doses of infliximab were not always necessary. Today, upon exercising the ‘treat-to-target’ initiative, tight control aimed at clinical remission was strongly recommended. He concluded that determining the infliximab dose before starting treatment may be a useful strategy to reach clinical remission at an earlier stage.
Biofree remission was then discussed by a presentation on the ‘Next stage of RA treatment’ by Yoshiya Tanaka (University of Occupational and Environmental health, Kitakyushu, Japan). Discontinuation of TNF-α inhibitors was an important issue from the view points of safety and economy, and the possibility of discontinuation has been reported particularly in early-stage RA patients (BeSt study). He reported on updated findings of an interim report of the Remission Induction by Remicade in RA (RRR) study given in 2009, which was undertaken to seek the possibility of discontinuing infliximab therapy in RA patients. This study included a total of 114 patients with RA who reached and maintained low disease activity (DAS28 <3.2) for more than 24 weeks with infliximab treatment who then agreed to discontinue the treatment. Among the 102 evaluable patients who completed the study, 56 maintained low disease activity after 1 year (RRR-achieved group) and showed no progression in radiologic damage and functional disturbance, and 44 remained in clinical remission (DAS28 <2.6). By logistic regression and receiver operating characteristic analysis, it was suggested that the cutoff point for achieving RRR at the time of patient enrollment was a DAS28 of 2.22, and a deep remission was necessary at the time of the discontinuation.
19 November 2011
The last day of the congress had six sessions; one of them was a parallel session on ‘Autoimmunity: pathogenetic mechanisms’ chaired by Shunle Chen (Shanghai JiaoTong University, Xuhui, China) and Sandra Navarra (University of Santo Tomas, Manila, Phillipines). The session started with a presentation on ‘Antiphospholipid syndrome: pathogenesis and genetics’ by Koike, which discussed the APS and the role of antiphospholipid antibodies in the disease. He demonstrated that mononuclear cells stimulated by monoclonal anti-β2GPI antibodies from APS patients induce phosphorylation of p38 MAPK and upregulation of tissue factor expression. He also assessed the profile of complement activation in patients with APS. The complement levels were clearly lower in patients with primary APS than those in controls with other rheumatic diseases. In addition, hypocomplementemia was correlated with anticoagulant activity and TNF-α levels. He concluded that both the complement system and the direct effect of antiphospholipid antibodies on monocytes or endothelial cells were most important for the pathophysiology of APS.
Chung-Tei Chou (General Hospital, Taipei, Taiwan, The Republic of China) presented the synovial immunopathologic study in ankylosing spondylitis (AS) and other rheumatic diseases. The study focused on the immunologic features of hip synovitis in AS and showed that the percentage of CD68+ cells in the sub-lining layer was significantly increased in AS compared with that in osteoarthritis. However, in the lining layer, there was significantly higher expression of matrix metalloproteinase-3 (MMP3) in AS than in osteoarthritis. In addition, they found that the increased number of CD68+ cells was correlated with the overexpression of MMP3 in the lining layer. This suggested that MMP3 and CD68+ cells play a significant role in the pathogenesis of synovial inflammation in AS.
The main highlight of the second parallel sessions was a session on immunoglobulin; the session was entitled ‘IVIg – an old, yet novel therapy for autoimmune diseases’ chaired by Zera Tellier (LFB Biotechnologies, Essonne, France) and Srini Kaveri (Paris Descartes University, Paris, France). The session opened with an introduction by Kaveri and was reviewed by Shoenfeld. A new aspect was presented by Donald Branch (Toronto General Hospital, Toronto, Canada) on ‘Is the mechanism of IVIg effect in autoimmune disease due to induction of IL-11?’ Intravenous immunoglobulin (IVIg) administered to mice with idiopathic thrombocytopenic purpura (ITP) due to passive administration of antiplatelet antibody resulted in the induction of IL-11 with an increase in thromobopoiesis and amelioration of the ITP. Administration of recombinant IL-11 partially resolved the ITP, and neutralizing anti-IL-11 partially prevented amelioration of the ITP following IVIg administration. However, when using IL-11R-/-, they observed no differences between the IL-11R-/- and wild-type mice to ameliorate ITP following IVIg administration. Although both mice were induced to produce IL-11, the IL-11R-/- mice were induced to produce increased amounts of thrombopoietin. Thus, it appears that the IL-11R-/- mice had a compensatory mechanism to respond to IVIg by producing increased amounts of thrombopoietin. Branch concluded that the IVIg effect was likely due, in part, to an increased induction of thrombopoietic cytokines such as IL-11 and/or thrombopoietin.
The last plenary session was chaired by Chou and Yoga I Kasjmir (Universitas Indonesia, Indonesia) entitled ‘Pearls and novel therapy, Treg cells and autoimmunity’. One of the most impressive last sessions was presented by Emese Kiss (National Institute of Rheumatology, Budapest, Hungary). He focused on the development and production of monoclonal antibodies manufactured by biotechnological methods and reviewed ‘The development of innovative targeted therapies with special attention to monoclonal antibodies’.
Conclusion
The 5th Asian Congress on Autoimmunity was a highly successful meeting. Not only was it a great experience for the young scientists, it was also a great time for the more experienced scientists. In contrast to other congresses, this congress was different and unique because there were lectures on both clinical and the basic science.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Reference
- Shoenfeld Y, Cervera R, Gershwin ME. Diagnostic Criteria in Autoimmune Diseases (Edition 1). Humana Press, NY, USA, 1–598 (2008).