V1.2. RECOGNITION OF MULTIPLE HSP60 EPITOPES IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS OPENS THE WAY FOR ANTIGEN-SPECIFIC IMMUNOTHERAPYV1.3. HUMAN HSP60 INDUCES REGULATORY T CELLS EXPRESSING CD30 IN THE REMITTING FORM OF JIAV1.4. FUNCTIONALlY SIGNIFICANT IL-6 ALLELIC ASSOCIATIONS IN SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS (SJIA)V1.5. STUDY OF THE INSULIN-LIKE GROWTH FACTOR-I (IGF-I) SYSTEM IN INTERLEUKIN-6 (IL-6) TRANSGENIC MICEV1.6. A NOVEL 5' FLANKING REGION POLYMORPHISM OF MACROPHAGE …
Authors: S. S. M. Kamphuis, I. de Kleer, R. Jeffery, C. Meazza, R. P. Donn, R. Cimaz, N. Ruperto, K. Davies, J. M. Gardner-Medwin, J. M. Gardner-Medwin, S. Seeliger, V. Vargova, R. Vesely, A. Ravelli, M. A. J. van Rossum, G. Simonini, E. Tsitsami, F. Kanakoudi-Tsakalidou, I. De Kleer, D. J. Lovell, G. Martini, A. Ravelli, S. Hagelberg, B. Fazeelat, H. W. Lehmann, P. Lahdenne, R. Brik, J. Frenkel, H. Ozdogan, G. Berglind-Dehlin, J. W. H. Custers, W. P. Bekkering, S. M. Maillard, T. Takken, J. M. Scott, W. de Jager, I. M. de Kleer, G. Gordon, E. Koffeman, M. Massa, A. Martini, G.T. Rijkers, W. van Eden, W. Kuis, A. B. J. Prakken, S. Albani, S. Kamphuis, W. de Jager, G. Gordon, N. Wulffraat, R. van der Zee, G. Rijkers, W. van Eden, B. Prakken, W. Kuis, L. Luong, E. Ogilvie, J. MacFadyen, S. Humphries, P. Woo, P. Pignatti, M. Vivarelli, S. Garrone, A Barreca, A Martini, F. De Benedetti, E. Shelley, W. Ollier, W. Thomson, P. L. Meroni, A. Brucato, L. Catelli, K. Goulene, M. Stramba-Badiale, None Ravelli, None Murray, None Gianni, None Lovell, None Tsitsami, None Feldman, None Silverman, None Machado, None Garay, None Andersson-Gare, None De Cunto, None Dolezalova, None Hashkes, None Honkanen, None Huppertz, None Joos, None Kuis, None Lilleby, None Melo-Gomes, None Ozdogan, None Prieur, None Rumba, None Susic, None Woo, None Martini, A. V. Ramanan, S. Sawhney, K. J. Murray, P. Dolezalova, T. R. Southwood, C. A. J. Ryder, T. R. Southwood, I. H. Engels, T. Vogl, C. Sorg, C. S. Underkötter, J. Roth., R. Vesely, A. Feketeova, M. Massa, F. De Benedetti, A. Ravelli, R. D'Alterio, V. Vargova, A. Martini, S. Magni Manzoni, T. Foti, C. Besana, E. Felici, L. Trail, S. Garay, E. Sala, A. Pistorio, A. Martini, A. H. Zwinderman, M. Boers, R. M. van Soesbergen, B. A. C. Dijkmans, P. F. Dijkstra, B. Porfirio, R. Cimaz, G. B. Calabri, F. Falcini, A. Ravelli, E. Bozzola, S. Magni Manzoni, S. Viola, C. Cugno, A. Pistorio, N. Ruperto, A. Martini, M. Trachana, P. Pratsidou-Gertsi, E. Tsitsami, C. Vasileiadis, D. Brinkman, G. Rijkers, B. Prakken, R. ten Cate, W. Kuis, N. Wulffraat, E. H. Giannini, M . Lange, D. J. Burge, B. K. Finck, D. Gobber, C. Agosto, A. Vianello, F. Zulian, C. Moretti, F. Temporini, F. Rossi, S. Magni Manzoni, S. Viola, G. Rossi, A. Pistorio, A. Martini, B. Magnusson, U. Andersson, C. A. J. Ryder, J. M. Gardner-Medwin, E. Sharif, N. Brown, G. Kingsley, T. R. Southwood, L. Kühner, K. Beckenlehner, K. G. Heide, R. M. Küster, S. Modrow, T. Heikkilä, J. Panelius, I. Seppälä, R. Gershoni-Baruch, M. Shinawi, L. Kastinez, A. Livneh, S. M. Houten, S. Mandey, G. T. Rijkers, H. R. Waterham, R. J. A. Wanders, W. Kuis, M. Melikoğlu, M. R. Altıparmak, N. Saylan, O. Kasapcopur, N. Arısoy, H. Yazıcı, A. Bredfelt, J. van der Net, P. J. M. Helders, R. ten Cate, M. A. J. van Rossum, T. P. M. Vliet Vlieland, C. Pilkington, K. J. Murray, J. van der Net, E. van Bostelen, N. H. M. J. van Veldhoven, P. J. M. Helders, J. Waterfield
Journal: Annals of the Rheumatic Diseases (2001)

Objective: We previously showed that in Juvenile Idiopathic Arthritis (JIA) patients human and bacterial heat shock protein 60 can be the target of (autoimmune) T cell responses. To determine potential target epitopes for immunotherapy, we needed to identify hsp60 epitopes recognized by a majority of JIA patients. The polymorphic HLA background in JIA has hampered this before.

Methods: With the usage of a novel computeralgorithm (Sette, Eppimmune, La Jolla, CA), predicting potential pan-DR binding sites on a given protein sequence, eight different T cell epitopes on both human and mycobacterial hsp60 have been identified and tested for T cell responses in JIA patients.

Results: All eight peptides yielded clear T cell responses (T cell proliferation and cytokine production), each in a majority (60-100%) of JIA patients. Interestingly we found production of TNF-α, IFN-γ and IL-10; the production of both IL-10 and IFN-γ strongly suggests the induction of regulatory T cells. One of the identified mycobacterial epitopes, had only minor changes compared tot the peptide that induced protection in Adjuvant Arthritis, and there was a clear correlation between the T cell response to this mycobacterial peptide and its human analogue. This underlines that we have found a subset of T cells crossreacting between self and non-self hsp60.

Conclusion: We have identified eight hsp60 epitopes recognized by a majority of JIA patients. The cytokine response induced by these peptides suggests the induction of regulatory T cells. Further analysis is currently being performed to unravel in detail the nature of the found T cell responses.

View this table:

Table 4-1 
Comparison of MIF –173 C/G allele frequencies (%) in JIA patients vs Controls



View this table:

Table 8-2 
Incidence of vasculitis (95% CI) per 100,000 children/year. *p<0.01 from other ethnic groups



# V1.3. HUMAN HSP60 INDUCES REGULATORY T CELLS EXPRESSING CD30 IN THE REMITTING FORM OF JIA {#article-title-2}

Of Juvenile Idiopathic Arthritis (JIA) the oligoarticular form has a relative benign clinical course, whereas polyarticular and systemic JIA are non-remitting, …