The chemokines IP-10/CXCL10 and IL-8/CXCL8 are potential novel biomarkers of warm autoimmune hemolytic anemia
Bibliographic record
Abstract
To date, little is known about what causes the breakdown of immune tolerance or the significance of increased cytokines found by some investigators in patients with warm autoimmune hemolytic anemia (wAIHA).[1][2][3][4][5][6] In this retrospective study, plasma was collected from 54 direct antiglobulin test (DAT)positive samples of patients with wAIHA, documented by the highly respected laboratory of the late George Garratty at the American Red Cross Blood Services, Southern California Region, Pomona, California.This reference laboratory specializes in confirmation of autoimmune hemolytic anemias by serological testing as having active or compensated wAIHA (supplemental Table S1 for clinical details).Plasma samples from 36 healthy controls (HC) obtained from the Canadian Blood Services, Toronto, were used for comparison.The samples were analyzed for 38 cytokines, chemokines, and growth factors as described in the supplemental Methods.Ethics approvals (CBS protocol for normal healthy donors #2009.015and American Red Cross Protocol for patients with wAIHA #2011-007) were obtained to do the study, which was conducted according to the Declaration of Helsinki.Using the samples from 54 patients, we identified a significant difference in 15 cytokines when compared with HC; an elevation of cytokines IL-1Ra, IL-6, IL-10, IL12p70, TNFα and chemokines IL-8/ CXCL8, IP-10/CXCL10, GRO/CXCL1, MCP-1/CCL2 and a decrease in cytokines IFNα2, IL-3, IL-13, TGFα and chemokines fractalkine/CX3CL1, MDC/CCL22 (supplemental Table S2 in supplemental Methods and Results for statistical methods and summary statistics for all cytokines analyzed).For subsequent analysis, we considered the stability of these 15 cytokines.Although our samples were stored as ethylenediaminetetraacetic acid (EDTA) whole blood for up to 6 days before having the plasma separated and stored, we previously determined that blood collected into EDTA anticoagulant maintains stability of many cytokines, even up to 10 days of storage.7 Applying the results of that storage study, we identified the following 7 (3 cytokines and 4 chemokines) from the 15 above that were stable in stored EDTA whole blood: IL-6, IL-10, TNFα, IL-8/CXCL8, IP-10/CXCL10, MCP-1/ CCL2, and MDC/CCL22 (Figure 1).Approximately half of the patients with wAIHA had a history of recent transfusion (past 3 months).Transfusion-related immunomodulation is well known, and its effects on circulating cytokine levels have been described.1 To examine whether transfusion status affects the change profile of the significant cytokines, we included this variable in the scatterplot representation of the data (Figure 1).We found IL-6, IL-8/CXCL8, IL-10, IP-10/CXCL10, MCP-1/CCL2, and TNFα significantly elevated in wAIHA compared with HC, whereas only the chemokine MDC/CCL22 was significantly decreased in our study (Figure 1).There have been 2 other studies that corroborate our findings for IL-6.One study using cultured peripheral blood mononuclear cell (PBMCs) from 28 patients with
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".