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Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH.

ABSTRACT: Serum soluble interleukin-2 receptor (sIL-2r) is an important disease marker in hemophagocytic lymphohistiocytosis (HLH), but there are no published data on its diagnostic value in adults. We conducted a single-center retrospective study of 78 consecutive adults who had sIL-2r measured for suspected HLH. Serum sIL-2r levels were measured by enzyme-linked immunosorbent assay (adult reference range, 241-846 U/mL). There were 38 patients with HLH and 40 with a non-HLH diagnosis (such as sepsis, liver disease, histiocyte disorders, autoimmune disease, leukemia, or lymphoma). The receiver operating characteristic curve demonstrated that sIL-2r is a good to excellent diagnostic test for adult HLH, with an area under the curve (AUC) of 0.90 (95% confidence interval, 0.83-0.97) compared with AUC 0.78 (95% confidence interval, 0.67-0.88) for ferritin. The optimal threshold for sIL-2r was 2515 U/mL (sensitivity, 100%; specificity, 72.5%). Although there was a large indeterminate range for sIL-2r, a level of 2400 U/mL or less was helpful for ruling out HLH (sensitivity, 100%), and more than 10?000 U/mL was helpful for ruling in HLH (specificity, 93%). Higher mean sIL-2r levels were seen in malignancy-associated HLH (20?241 U/mL) compared with infection-associated HLH and macrophage activation syndrome (9720 and 5008 U/mL, respectively; P < .05). Levels above 10?000 U/mL were not associated with worse prognosis in patients with HLH. Serum sIL-2r is a sensitive test for diagnosis of adult HLH, but is not as specific as previously reported in children. Additional studies enriched with patients without HLH who have conditions associated with T-cell activation, such as lymphoma and autoimmune lymphoproliferative syndrome, are needed.

SUBMITTER: Hayden A

PROVIDER: S-EPMC5728644 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH.

Hayden Anna A Lin Molly M Park Sujin S Pudek Morris M Schneider Marion M Jordan Michael B MB Mattman Andre A Chen Luke Y C LYC

Blood advances 20171206 26

Serum soluble interleukin-2 receptor (sIL-2r) is an important disease marker in hemophagocytic lymphohistiocytosis (HLH), but there are no published data on its diagnostic value in adults. We conducted a single-center retrospective study of 78 consecutive adults who had sIL-2r measured for suspected HLH. Serum sIL-2r levels were measured by enzyme-linked immunosorbent assay (adult reference range, 241-846 U/mL). There were 38 patients with HLH and 40 with a non-HLH diagnosis (such as sepsis, liv ...[more]

PMID: 29296904

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Project description:INTRODUCTION: There has been no report in the literature of a soluble form of interleukin (IL)-18 receptor ? (IL-18R?). In this study, we evaluated the levels and characteristics of soluble IL-18R? (sIL-18R?) in the sera of patients with rheumatoid arthritis (RA) and compared these results to control populations. METHODS: The sIL-18R? complex was isolated from pooled human blood serum using an anti-IL-18R? monoclonal antibody affinity column. The purified sIL-18R? was then examined using Western blot analysis and used in experiments to evaluate the effects on an IL-18-responsive natural killer (NK) human cell line, NK0. An enzyme-linked immunosorbent assay was developed, and sera from 145 patients with RA, 6 patients with adult-onset Still's disease, 31 patients with osteoarthritis (OA), 39 patients with systemic lupus erythematosus (SLE) and 67 controls were tested, along with levels of immunoglobulin M, rheumatoid factor, anticyclic citrullinated peptide antibody, IL-18, IL-13 and interferon (IFN)-?. Area under the receiver operating characteristic curve (ROC-AUC) analysis was used to evaluate the diagnostic utility of the sIL-18R? complex. RESULTS: The isolated sIL-18R? complex can be associated with IL-18 and the soluble form of the IL-18R? chain. The sIL-18R? complex bound to the surface to the NK0 cell line, antagonized the stimulatory effects of IL-18 and IL-2 on the NK0 cell line and inhibited IFN-? production by the cells. The serum levels of sIL-18R? complex in RA (186.0 ± 33.5 ng/mL, n = 145) and adult-onset Still's disease (98.2 ± 8.9 ng/mL, n = 6) were significantly (P < 0.001) higher than those in the healthy controls (52.3 ± 8.5 ng/mL, n = 67), OA (38.6 ± 5.4 ng/mL, n = 31), SLE (44.6 ± 3.2 ng/mL, n = 39). The serum level of sIL-18R? complex was not significantly different between RA and adult-onset Still's disease patients. The serum levels of IL-18, IL-13 and IFN-? in the RA patients were significantly (P < 0.01) higher than in OA and SLE patients as well as healthy controls. ROC-AUC analysis of the serum concentration of sIL-18R? indicated that it was significantly diagnostic of RA. Moreover, a tumor necrosis factor inhibitor, etanercept, significantly (P < 0.0001) decreased levels of sIL-18R? in the sera of 29 RA patients 6 months after treatment. CONCLUSIONS: The sIL-18R? complex could be a potentially useful biomarker for the diagnosis of RA.

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Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH.

Publications

Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH.

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