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Interleukin-18–607 Promoter Polymorphism in Sarcoidosis: Ignoring "Negative" Results

We would like to thank Dr. Janssen and colleagues for their interest in our article (1). Unfortunately, a number of the points they raise are incorrect. They criticize our published study for having a small number of patients (n = 94). However, in the study by Janssen and coworkers (2), which they champion, there were 133 patients, of which only 94 were deemed "true" sarcoid. The primary focus of our article was to report the potential role for gram-negative colonization in sarcoidosis. The interleukin-18–607^A/C single nucleotide polymorphism (SNP) data, while interesting, did not impact significantly on that finding and, although our genetic analysis gave a positive correlation, we felt, along with others, that it is vitally important to examine the functional consequences of any SNP. Because our functional analysis did not find any difference between the A and C alleles, we have shown that, in the context of endotoxin, the –607^A/C allele does not play a functional pathogenic role in sarcoidosis. We agree that we should have cited Janssen and coworkers' article (2) and would like to assure them that we were not participating in the conspiracy they call "the citation bias." Finally, we could not cite Zhou and coworkers' article (3) as it was not published prior to submission of our own revised and accepted manuscript in June, 2005.

Deirdre Kelly, Catherine Greene, Gerard Meachery, Michael O'Mahony, Paula Gallagher, Clifford Taggart, Shane O'Neill and Noel G. McElvaney

Royal College of Surgeons in Ireland, Dublin, Ireland

FOOTNOTES

Conflict of Interest Statement: D.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. G.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.O. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.O. spoke at conferences sponsored by AstraZeneca, Merck, Sharp and Dohme, and Boehringer Ingelheim. He also received industry-supported grants from AstraZeneca. N.G.M. acted as consultant to Aventis Behring and Baxter Biosciences and served on the advisory board for Genaera. He received research grants for participating in multicenter clinical trials from Genaera and from Aventis Behring.

REFERENCES

1. Kelly DM, Greene CM, Meachery G, O'Mahony M, Gallagher PM, Taggart CC, O'Neill SJ, McElvaney NG. Endotoxin up-regulates interleukin-18: potential role for gram-negative colonization in sarcoidosis. Am J Respir Crit Care Med 2005;172:1299–1307.[Abstract/Free Full Text]
2. Janssen R, Grutters JC, Ruven HJ, Zanen P, Sato H, Welsh KI, du Bois RM, van den Bosch JM. No association between interleukin-18 gene polymorphisms and haplotypes in Dutch sarcoidosis patients. Tissue Antigens 2004;63:578–583.[CrossRef][Medline]
3. Zhou Y, Yamaguchi E, Hizawa N, Nishimura M. Roles of functional polymorphisms in the interleukin-18 gene promoter in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:105–113.[Medline]

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