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Therapeutic Apheresis and Dialysis 11(1):78–79 doi:10.1111/j.1744-9987.2007.00458.x © 2007 International Society for Apheresis 78 Blackwell Publishing AsiaMelbourne, AustraliaTAPTherapeutic Apheresis and Dialysis1744-9979© 2006 The Author(s); Journal compilation © 2006 International Society for Apher- esis?2007 111 7879Letter to the Editor Letter to the EditorLetter to the Editor Communications This journal welcomes comments from all those involved, as researchers, developers or users, in therapeutic apheresis and dialysis. We would like to hear of your experiences. Please send all communications to the Editorial Office. Letter to the Editor Can Serological Tests Tell Us Something About Latent Tuberculosis in Hemodialysis Patients? Dear Editor, We read the article by Yanai et al. which was published in your journal (1). The worth of anti- lipoarabinomannan antibody (anti-LAM) test in hemodialysis (HD) patients was evaluated. A rela- tionship between anti-LAM test and tuberculin skin test (TST) was not detected, but interestingly the anti- LAM positivity was significantly higher in patients with findings of old tuberculosis (TB) on the chest X- ray. Bacillus Calmette-Guerin (BCG) vaccination during childhood was incriminated for the results and the high positive rate of anti-LAM in asymptomatic HD patients indicated the need for careful interpre- tation for diagnosing the mycobacterial infection. We also examined the value of anti-LAM antibod- ies for the diagnosis of latent TB in HD patients (2). Latent TB is a serious problem in this immunodefi- cient population because of the increased risk for TB reactivation. TST is inaccurate. Anti-LAM detection theoretically has two advantages, because LAM is a lipoglycan and it is quite possible for it to behave like a T-cell–independent antigen (3). First, in contrary to impaired immune response to T-cell-dependent anti- gens, which is responsible for the high incidence of anergy in skin testing, antibody response to T-cell– independent antigens is only moderately suppressed in HD patients (4). Second, T-cell–independent anti- gen-induced antibody response lacks long-lasting memory (5). In the 74 HD patients of our study, who were never treated for TB, a strong association was detected between results of the TST and anti-LAM test sug- gesting that the anti-LAM test could be a useful tool for diagnosing latent TB. A similar association was found in 48 healthy volunteers. In 21 TST-positive renal transplant candidates on HD who had com- pleted preventive anti-TB treatment, a positive TST and negative anti-LAM test was a constant finding suggesting that immune response to LAM lacks long- lasting memory, a feature of T-cell-independent anti- gens. Thus, an anti-LAM test can distinguish latent TB from a previous eradicated TB infection that did not proceed to latency, and it is relatively indepen- dent from a prior BCG vaccination. Finally, a nega- tive anti-LAM test might reflect the absence of latent TB, even in patients with a positive TST. The discrepancy between the two studies is not surprising for two reasons. First, in our study TST was considered positive if the induration was larger than 10 mm for HD patients and larger than 15 mm for healthy volunteers, according to the Centers for Dis- ease Control and Prevention, USA. Yanai et al. con- sidered as positive any erythema larger than 10 mm, even in the absence of induration. 71.6% of their TST positive patients would be considered as TST nega- tive in our study. Second, although we both used the same semiquantitative immunochromatographic assay (MycoDot; Mossman Associates, Blackstone, USA), because our aim was not to diagnose active TB, but to screen for latent TB, which most likely is characterized by a lower anti-LAM titer than active TB, we used a serum dilution smaller than the man- ufacturer’s proposed dilution. Finally, in order to diminish the effect of BCG vaccination on TST

Can Serological Tests Tell Us Something About Latent Tuberculosis in Hemodialysis Patients?

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Therapeutic Apheresis and Dialysis 11(1):78–79doi:10.1111/j.1744-9987.2007.00458.x© 2007 International Society for Apheresis

78

Blackwell Publishing AsiaMelbourne, AustraliaTAPTherapeutic Apheresis and Dialysis1744-9979© 2006 The Author(s); Journal compilation © 2006 International Society for Apher-esis?2007

111

7879Letter to the Editor

Letter to the EditorLetter to the Editor

Communications

This journal welcomes comments from all those involved, as researchers, developers or users, in therapeutic apheresis and dialysis. We would like to hear of your experiences. Please send all communications to the Editorial Office.

Letter to the Editor

Can Serological Tests Tell Us Something About Latent Tuberculosis in Hemodialysis Patients?

Dear Editor,We read the article by Yanai et al. which was

published in your journal (1). The worth of anti-lipoarabinomannan antibody (anti-LAM) test inhemodialysis (HD) patients was evaluated. A rela-tionship between anti-LAM test and tuberculin skintest (TST) was not detected, but interestingly the anti-LAM positivity was significantly higher in patientswith findings of old tuberculosis (TB) on the chest X-ray. Bacillus Calmette-Guerin (BCG) vaccinationduring childhood was incriminated for the results andthe high positive rate of anti-LAM in asymptomaticHD patients indicated the need for careful interpre-tation for diagnosing the mycobacterial infection.

We also examined the value of anti-LAM antibod-ies for the diagnosis of latent TB in HD patients (2).Latent TB is a serious problem in this immunodefi-cient population because of the increased risk for TBreactivation. TST is inaccurate. Anti-LAM detectiontheoretically has two advantages, because LAM is alipoglycan and it is quite possible for it to behave likea T-cell–independent antigen (3). First, in contrary toimpaired immune response to T-cell-dependent anti-gens, which is responsible for the high incidence ofanergy in skin testing, antibody response to T-cell–independent antigens is only moderately suppressedin HD patients (4). Second, T-cell–independent anti-gen-induced antibody response lacks long-lastingmemory (5).

In the 74 HD patients of our study, who were nevertreated for TB, a strong association was detectedbetween results of the TST and anti-LAM test sug-

gesting that the anti-LAM test could be a useful toolfor diagnosing latent TB. A similar association wasfound in 48 healthy volunteers. In 21 TST-positiverenal transplant candidates on HD who had com-pleted preventive anti-TB treatment, a positive TSTand negative anti-LAM test was a constant findingsuggesting that immune response to LAM lacks long-lasting memory, a feature of T-cell-independent anti-gens. Thus, an anti-LAM test can distinguish latentTB from a previous eradicated TB infection that didnot proceed to latency, and it is relatively indepen-dent from a prior BCG vaccination. Finally, a nega-tive anti-LAM test might reflect the absence of latentTB, even in patients with a positive TST.

The discrepancy between the two studies is notsurprising for two reasons. First, in our study TST wasconsidered positive if the induration was larger than10 mm for HD patients and larger than 15 mm forhealthy volunteers, according to the Centers for Dis-ease Control and Prevention, USA. Yanai et al. con-sidered as positive any erythema larger than 10 mm,even in the absence of induration. 71.6% of their TSTpositive patients would be considered as TST nega-tive in our study. Second, although we both usedthe same semiquantitative immunochromatographicassay (MycoDot; Mossman Associates, Blackstone,USA), because our aim was not to diagnose activeTB, but to screen for latent TB, which most likely ischaracterized by a lower anti-LAM titer than activeTB, we used a serum dilution smaller than the man-ufacturer’s proposed dilution. Finally, in order todiminish the effect of BCG vaccination on TST

Letter to the Editor 79

© 2007 International Society for Apheresis Ther Apher Dial, Vol. 11, No. 1, 2007

results, we excluded subjects vaccinated during thelast 15 years (6). Only a few HD patients wereexcluded. Besides that, the anti-LAM test seems tobe affected less by BCG vaccination than by TST.

In our opinion, serological tests for the diagnosisof latent TB in HD patients are promising.

Theodoros Eleftheriadis,1 Georgia Antoniadi,1

Vassilis Liakopoulos,2 Ioannis Stefanidis,2 andVassilis Vargemezis3

1Renal Unit, General Hospital of Serres, Serres,2Nephrology Department, University Hospital ofLarissa, Larissa, and 3Nephrology Department,University Hospital of Thrace, Alexandroupolis,

GreeceEmail: [email protected]

REFERENCES

1. Yanai M, Uehara Y, Takeuchi M et al. Evaluation of serologicaldiagnosis tests for tuberculosis in hemodialysis patients. TherApher Dial 2006;10:278–81.

2. Eleftheriadis T, Tsiaga P, Antoniadi G et al. The value of serumantilipoarabinomannan antibody detection in the diagnosis oflatent tuberculosis in hemodialysis patients. Am J Kidney Dis2005;46:706–12.

3. Chatterjee D, Khoo KH. Mycobacterial lipoarabinomannan:an extraordinary lipoheteroglycan with profound physiologicaleffects. Glycobiology 1998;8:113–20.

4. Robinson J. Efficacy of pneumococcal immunization in patientswith renal disease—What is the data? Am J Nephrol 2004;24:402–9.

5. Weintraub A. Immunology of bacterial polysaccharide anti-gens. Carbohydr Res 2003;338:2539–47.

6. Wang L, Turner MO, Elwood RK, Schulzer M, FitzGerald JM.A meta-analysis of the effect of bacilli Calmette-Guérin vacci-nation on tuberculin skin test measurements. Thorax 2002;57:804–9.