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Clinical and Diagnostic Laboratory Immunology, February 2005, p. 366, Vol. 12, No. 2
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.2.366.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Variability of the RNase L Isoform Ratio (37 Kilodaltons/83 Kilodaltons) in Diagnosis of Chronic Fatigue Syndrome

	LETTER

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In order to evaluate the variability and reproducibility of the 37/83 R in the diagnosis of CFS, we assayed it in duplicate as described by Demettre et al. (2) once a month for 3 months with nine patients fulfilling CFS criteria (mean age ± standard deviation = 43.1 ± 10.4 years). The accuracy of this ratio in the diagnosis of CFS was also tested and correlated with a clinical tool, the Multidimensional Fatigue Inventory (MFI) score, in a case-control study involving 28 CFS patients (mean age, 43.1 ± 10.4 years; MFI, 60.9 ± 14.6) and 24 healthy volunteers (mean age, 40.5 ± 9.9 years; MFI, 27.1 ± 7.7).

The results of these two assays were correlated by the Spearman test for each sample; the means of the results of the assays were calculated, and the results from 3 consecutive months were correlated. Sensitivities, specificities, and positive and negative prognostic values were calculated with different threshold ratios of RNase L isoforms (0.4, 0.45, and 0.5). Ninety-five percent confidence intervals (95% CIs) were estimated. The ages of subjects in the two groups were comparable, and the MFI scores of the CFS group were higher than those of the control group (Mann-Whitney U test; P < 0.05).

The correlation between two 37/83 R assays from the PBMC sample was lower for the CFS group than for the control group. Moreover, the correlation decreased with time (r = 0.69, 0.69, and 0.33 at the first, second, and third months, respectively) for the CFS group while staying unchanged for the control group (r = 0.95). The correlations between two average results of 37/83 R at two different months were low. The correlations between the two first two months, the second and third months, and the first and third months were 0.16, 0.14, and –0.03, respectively. The 37/83 R cutoff of 0.4 yielded the best discrimination of CFS patients from controls, with 78.6% sensitivity (95% CI, 20.5 to 46.1%) and 33.3% specificity (95% CI, 46.2 to 72.8%). The positive and negative prognostic values were 59.5% (95% CI, 67.5 to 89.7%) and 53.3% (95% CI, 39.7 to 66.9%), respectively. Finally, the correlations between the MFI and 37/83 R were very weak: 0.14 at the first month, 0.51 at the second month, and -0.3 at the last month.

Our data suggest a high variability and poor reproducibility of the 37/83 R for CFS patients and variations of the 37 kDa/83kDa R results while fatigue remains stable. This variability might be due to the increased proteolytic activity reported for PMBC of patients with CFS (2). Thus, we draw attention to the use of this test. The small sample size of this study could have lowered some correlations, but could not have lowered the variability results.

	REFERENCES

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1. De Meirleir, K., C. Bisbal, I. Campine, P. De Becker, T. Salehzada, E. Demettre, and B. Lebleu. 2000. A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome. Am. J. Med. 108:99-105.[Medline]
2. Demettre, E., L. Bastide, A. D'Haese, K. De Smet, K. De Meirleir, K. P. Tiev, P. Englebienne, and B. Lebleu. 2002. Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J. Biol. Chem. 277:35746-35751.[Abstract/Free Full Text]
3. Tiev, K. P., E. Demettre, P. Ercolano, L. Bastide, B. Lebleu, and J. Cabane. 2003. RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome. Clin. Diagn. Lab. Immunol. 10:315-316.[Abstract/Free Full Text]

This article has been cited by other articles:

• Fremont, M., Vaeyens, F., Herst, C. V., De Meirleir, K., Englebienne, P., Tiev, K. P., Cabane, J., Lebleu, B. (2005). 37-Kilodalton/83-Kilodalton RNase L Isoform Ratio in Peripheral Blood Mononuclear Cells: Analytical Performance and Relevance for Chronic Fatigue Syndrome. CVI 12: 1259-1260 [Full Text]  

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