Limitations of human t-lymphotropic virus type 1 antibody testing in hospitals of endemic regions in China

Abstract

Purpose: This study aims to evaluate the sensitivity and specificity of human T-lymphotropic virus type 1 (HTLV-1) antibody testing within hospitals located in HTLV-1 endemic areas of China.

Method: We performed a retrospective analysis of the clinical records and laboratory results for 1,147 patients who underwent HTLV-1 antibody testing using the Wantai HTLV-1 antibody detection kit and Polymerase Chain Reaction (PCR) testing for HTLV-1 nucleic acids, at Fujian Medical University Union Hospital between 2017 and 2023.

Result: The study population comprised 674 males (58.8%) and 473 females (41.2%), with an age distribution ranging from 7 to 86 years, and a median age of 50 years. Of the patients, 81 (7.1%) tested positive for HTLV-1 antibodies, including 39 males and 42 females. Predominantly, these positive cases were identified within the hematology department (93.8%). The cases originated from several high-prevalence coastal regions in Fujian province, such as Pingtan Island, Fuqing, Changle, Lianjiang, Fuan, Shouning, Xiapu, Zhouning, Fuding, Jiaocheng, Xiuyu, and Licheng. According to current standards for interpreting positive results, only 79.6% of patients with adult T-cell leukemia/lymphoma (ATLL) confirmed by HTLV-1 nucleic acid testing presented positive antibody results. Comparison of HTLV-1 antibody and nucleic acid test results revealed that the antibody test possessed a sensitivity of 63.0% and a specificity of 94.8%. A receiver operating characteristic (ROC) curve analysis determined that a threshold of 0.335 signal-to-cutoff (S/CO) was optimal for classifying positive antibody test results, yielding a sensitivity of 86.3% and a specificity of 94.4%.

Conclusion: The Wantai HTLV-1 antibody test kit, when utilized in hospitals within endemic regions, exhibits a high level of specificity. However, its sensitivity is found to be lacking when evaluated against the current standards for the interpretation of positive results. For patients with a high clinical suspicion of HTLV-1 infection-related diseases, it is crucial to conduct testing of HTLV-1 antibodies and nucleic acids.

Keywords: antibodies; epidemiology; hematology; human T-lymphotropic virus type 1; nucleic acid testing.

Figure 1

Distribution of Patients’ Living Areas. A map depicting the geographical distribution of the patients’ living areas in Fujian province, highlighting the coastal regions of Pingtan Island, Fuqing, Changle, Lianjiang, Fuan, Shouning, Xiapu, Zhouning, Fuding, Jiaocheng, Xiuyu, and Licheng with a higher prevalence of HTLV-1. NA: no data was available because no patient from this region was tested for HTLV-1.

Figure 2

ROC Curve Analysis of HTLV-1 Antibody Testing. This figure presents a ROC curve analysis for HTLV-1 antibody testing, depicting the relationship between the sensitivity and specificity of various threshold values. The results of HTLV-1 nucleic acid testing served as the reference standard, with patients testing positive for HTLV-1 nucleic acid being classified as true positive cases. The optimal cut-off value, which maximizes the area under the ROC curve, is indicated by a dashed line at a S/CO ratio of 0.335.

Figure 3

Results of Antibody and Nucleic Acid Testing of HTLV-1. A scatter plot summarizing the results of HTLV-1 antibody and nucleic acid testing in the study population, showing the positive and negative rates for each testing method. Reference value: positive judgment criteria described by HLTV-1 test kit; optimal value: positive judgment criteria adjusted with ROC curve.

Figure 4

Results of Antibody and Nucleic Acid Testing of HTLV-1 in Patients with T-Cell Lymphoma/Leukemia or Suspected with HAM/TSP. (A) A scatter plot of results for patients with T-cell lymphoma/leukemia, showing the distribution of positive and negative antibody and nucleic acid test results. (B) A scatter plot of results for patients suspected with HAM/TSP, illustrating the distribution of positive and negative antibody and nucleic acid test results. Reference value: positive judgment criteria described by HLTV-1 test kit; optimal value: positive judgment criteria adjusted with ROC curve.

Figure 5

Follow-up of HTLV-1 Antibody and Nucleic Acid. A series of graphs depicting the dynamic changes in HTLV-1 antibody and nucleic acid levels over time in various patient cohorts. (A) A HTLV-1 carrier showing persistent positive results. (B-D) Three patients with ATLL, each showing persistent positive antibody and nucleic acid results. (E, F) Two patients with ATLL who received allo-HSCT, with transient negative nucleic acid results post-transplant but persistent positive antibody results. Reference value: positive judgment criteria described by HLTV-1 test kit; optimal value: positive judgment criteria adjusted with ROC curve.