التفاصيل البيبلوغرافية
| العنوان: |
Primary Sjögren's syndrome and deficiency of ICA69. |
| المؤلفون: |
Winer, Shawn, Astsaturov, Igor, Cheung, Roy, Tsui, Hubert, Song, Aihua, Gaedigk, Roger, Winer, Daniel, Sampson, Anastasia, McKerlie, Colin, Bookman, Arthur, Dosch, H-Michael |
| المصدر: |
Lancet (0099-5355); Oct2002, Vol. 360 Issue 9339, p1063, 7p |
| مستخلص: |
Background Sjo¨gren's syndrome is a common (about 1% of the population) autoimmune disease of salivary and lacrimal glands. Its cause and pathogenesis are poorly understood, and treatments are mostly for symptoms of the disease. ICA69 is a self-antigen expressed in brain, pancreas, salivary, and lacrimal glands. NOD-strain mice are an animal model of spontaneous Sjo¨gren's syndrome. We aimed to assess the role of ICA69 in autoimmunity against Sjo¨gren's syndrome.Methods We inactivated the genomic ICA69 locus, generated NOD congenic mice that were deficient in ICA69, and assessed development of Sjo¨gren's syndrome. ICA69 autoimmunity was investigated in controls and in patients with primary Sjo¨gren's syndrome or systemic lupus erythematosus, and in various NOD mice, some of which were given an ICA69-directed prototype peptide vaccine.Findings Disruption of the ICA69 locus prevented lacrimal gland disease and greatly reduced salivary gland disease in NOD mice. In healthy NOD mice, ICA69-specific T cells accumulated in lymph nodes that drain salivary tissue. T-cell and B-cell autoreactivity against ICA69 was much the same in patients with primary Sjo¨gren's syndrome, but not in those with systemic lupus erythematosus or in healthy controls. Immunotherapy with a high-affinity mimicry peptide targeting ICA69-specific T-cells reduced established Sjo¨gren's syndrome in wild-type NOD mice in the long term.Interpretation ICA69 is a new autoantigen in primary Sjo¨gren's syndrome that has an important role in progression of disease and could be of diagnostic value. Immunotherapy of primary Sjo¨gren's syndrome is promising, since autoimmunity in NOD mice with Sjo¨gren's syndrome seems to be uniquely susceptible to such treatment even late in disease. [Copyright &y& Elsevier] |
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