A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.
Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2010
|
| _version_ | 1797093277017571328 |
|---|---|
| author | McKinney, E Lyons, P Carr, E Hollis, J Jayne, DR Willcocks, L Koukoulaki, M Brazma, A Jovanovic, V Kemeny, D Pollard, A Macary, P Chaudhry, A Smith, K |
| author_facet | McKinney, E Lyons, P Carr, E Hollis, J Jayne, DR Willcocks, L Koukoulaki, M Brazma, A Jovanovic, V Kemeny, D Pollard, A Macary, P Chaudhry, A Smith, K |
| author_sort | McKinney, E |
| collection | OXFORD |
| description | Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity. |
| first_indexed | 2024-03-07T03:58:00Z |
| format | Journal article |
| id | oxford-uuid:c387f3e1-c0dd-4e26-a0bb-786dfe501039 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:58:00Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:c387f3e1-c0dd-4e26-a0bb-786dfe5010392022-03-27T06:17:09ZA CD8+ T cell transcription signature predicts prognosis in autoimmune disease.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c387f3e1-c0dd-4e26-a0bb-786dfe501039EnglishSymplectic Elements at Oxford2010McKinney, ELyons, PCarr, EHollis, JJayne, DRWillcocks, LKoukoulaki, MBrazma, AJovanovic, VKemeny, DPollard, AMacary, PChaudhry, ASmith, KAutoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity. |
| spellingShingle | McKinney, E Lyons, P Carr, E Hollis, J Jayne, DR Willcocks, L Koukoulaki, M Brazma, A Jovanovic, V Kemeny, D Pollard, A Macary, P Chaudhry, A Smith, K A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. |
| title | A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. |
| title_full | A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. |
| title_fullStr | A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. |
| title_full_unstemmed | A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. |
| title_short | A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. |
| title_sort | cd8 t cell transcription signature predicts prognosis in autoimmune disease |
| work_keys_str_mv | AT mckinneye acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT lyonsp acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT carre acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT hollisj acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT jaynedr acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT willcocksl acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT koukoulakim acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT brazmaa acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT jovanovicv acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT kemenyd acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT pollarda acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT macaryp acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT chaudhrya acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT smithk acd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT mckinneye cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT lyonsp cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT carre cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT hollisj cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT jaynedr cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT willcocksl cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT koukoulakim cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT brazmaa cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT jovanovicv cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT kemenyd cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT pollarda cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT macaryp cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT chaudhrya cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease AT smithk cd8tcelltranscriptionsignaturepredictsprognosisinautoimmunedisease |