Despite the established evidence of the strong negative effect exerted by PTPN22*T1858 allele on the immune system, conferring high susceptibility to a large subset of autoimmune diseases, we report a lack of association of PTPN22 1858C[T polymorphism with human longevity. Thus, the ability to survive to old age and to reach even exceptional life expectancy is largely unaffected by the genetically determined efficacy of the PTPN22-based immune response. On the other hand, it is noteworthy that the autoimmunity high-risk PTPN22*T1858 allele has been previously associated with a significant protective effect on Mycobacterium tuberculosis infection [30, 31]. This is an interesting fact since the burden of tuberculosis in the elderly is likely to continue to increase substantially [32]. Therefore, our results suggest that PTPN22*T1858 allele is not negatively selectedGenetic predisposition to produce high levels of IL is detrimental for longevity. Eur J Immunol: Hasegawa K, Martin F, Huang G, Tumas D, Diehl L, Chan AC (2004) PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells. Science: Gomez LM, Anaya JM, Martin J (2006) Genetic influence of PTPN R W polymorphism in tuberculosis. Hum Immunol: Lamsyah H, Rueda B, Baassi L, Elaouad R, Bottini N, Sadki K et al (2008) Association of PTPN gene functional variants with development of pulmonary tuberculosis in Moroccan population. Tissue Antigens: Tocque K, Bellis MA, Tam CM, Chan SL, Syed Q, Remmington T et al (2001) Long-term trends in tuberculosis. Comparison of age-cohort data between Hong Kong and England and Wales. Am J Respir Crit Care Med: Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottavini E et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci: Ammendola M, Bottini N, Pietropolli A, Saccucci P, Gloria-Bottini F (2011) Association between PTPN and endometriosis. Fertil Steril: Latiano A, Palmieri O, Valvano MR, Bossa F, Latiano T, Corritore G et al (2013) Evaluating the role of genetic variations of PTPN , NFKB , and FRIIIA genes in inflammatory bowel disease: a meta-analysis. Inflamm Bowel Dis: Petrone A, Suraci C, Capizzi M, Giaccari A, Bosi E, Tiberti C et al (2013) The protein tyrosine phosphatase nonreceptor (PTPN) is associated with high GAD antibody titer in latent autoimmune diabetes in adults: Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study Diabetes Care: Palacios EH, Weiss A (2004) Function of the Src-family kinases, Lck and Fyn in T-cell development and activation. Oncogene: Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M et al (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet: Ladner MB, Bottini N, Valdes AM, Noble JA (2005) Association of the single nucleotide polymorphism C T of the PTPN gene with type diabetes. Hum Immunol: Onengut-Gumuscu S, Ewens KG, Spielman RS, Concannon P (2004) A functional polymorphism (C/T) in the PTPN gene is linked and associated with type I diabetes in multiplex families. Genes Immun: Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC et al (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN) is associated with rheumatoid arthritis. Am J Hum Genet: Chung SA, Criswell LA (2003) PTPN: its role in SLE and autoimmunity. Autoimmunity: Vang T, Miletic AV, Bottini N, Mustelin T (2007) Protein tyrosine phosphatase PTPN in human autoimmunity. Autoimmunity: Rieck M, Arechiga A, Onengut-Gumuscu S, Greenbaum C, Concannon P, Buckner JH (2007) Genetic variation in PTPN corresponds to altered function of T and B lymphocytes. J Immunol: Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res: Sokal RR, Rohlf JF (1995) Biometry. WH Freeman eds, New York Saccucci P, Del Duca E, Rapini N, Verrotti A, Piccinini S, Maccari A et al (2011) Association between PTPN C T and type diabetes: a replication in continental Italy. Tissue Antigens: Candore G, Colonna-Romano G, Balistreri CR, Di Carlo D, Grimaldi MP, Liste F et al (2006) Biology of longevity: role of the innate immune system. Re