The role of lymphocyte proliferation tests in assessing occupational sensitization and disease

Current Opinion in Allergy and Clinical Immunology

Volumn 12, Issue 2, 2012, Pages 102-110

  Hines, Stella E ^a   Pacheco, Karin ^b,c   Maier, Lisa A ^b,c,d  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c Food Science and Human Nutrition   (United States)

^d UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

beryllium; chronic beryllium disease; contact allergy; lymphocyte proliferation test; occupational surveillance; sensitization

Indexed keywords

BERYLLIUM; CHROMIUM; CONTACT ALLERGEN; IMMUNOSUPPRESSIVE AGENT;

BERYLLIOSIS; CHRONIC BERYLLIUM DISEASE; CONTACT ALLERGY; DISEASE COURSE; DISEASE SEVERITY; ENDOPROSTHESIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; HYPERSENSITIVITY; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE PROLIFERATION; OCCUPATIONAL EXPOSURE; PRIORITY JOURNAL; REVIEW; SENSITIZATION;

ALLERGENS; ANIMALS; BERYLLIOSIS; BERYLLIUM; CHRONIC DISEASE; FEMALE; HUMANS; HYPERSENSITIVITY; LYMPHOCYTE ACTIVATION; MALE; MICE; O-PHTHALALDEHYDE; OCCUPATIONAL DISEASES; OCCUPATIONAL EXPOSURE;

EID: 84858159329     PISSN: 15284050     EISSN: 14736322     Source Type: Journal    
DOI: 10.1097/ACI.0b013e3283511396     Document Type: Review

References (91)

1. Samuel G, Maier LA. Immunology of chronic beryllium disease. Curr Opin Allergy Clin Immunol 2008; 8:126-134. (Pubitemid 351654307)
2. Department of Energy (US). Chronic Beryllium Disease Prevention Program, Final Rule. Code of Federal Regulations 1999. Title 10, vol 64, part 850, subpart 23.
3. Frome EL, Newman LS, Cragle DL, et al. Identification of an abnormal beryllium lymphocyte proliferation test. Toxicology 2003; 183:39-56. (Pubitemid 36005388)
4. Wambuch P. Beryllium lymphocyte proliferation testing (BeLPT). Springfield, Virginia: National Technical Information Service; 2001. Document No. DOESPEC-1142-2001.
5. Basketter DA. Skin sensitization: strategies for the assessment and management of risk. Br J Dermatol 2008; 159:267-273. (Pubitemid 352009829)
6. .Anderson SE, Umbright C, Sellamuthu R, et al. Irritancy and allergic responses induced by topical application of ortho-phthalaldehyde. Toxicol Sci 2010; 115:435-443. This article shows that an emerging popular substitute for the sensitizer glutaraldehyde, ortho-phthalaldehyde, shows clear evidence for sensitizing potential in LLNA. Workers exposed to this agent might benefit from medical surveillance for sensitization via LPT.
7. National Institute of Environmental Health Science. The murine local lymph node assay: a test method for assessing the allergic contact dermatitis potential of chemicals/compounds. Fed Regist 1999; 64:14006-14007.
8. Kreiss K, Mroz MM, Zhen B, et al. Epidemiology of beryllium sensitization and disease in nuclear workers. Am Rev Respir Dis 1993; 148 (4 Pt 1):985-991. (Pubitemid 23301218)
9. Kreiss K, Wasserman S, Mroz MM, Newman LS. Beryllium disease screening in the ceramics industry: blood lymphocyte test performance and exposure-disease relations. J Occup Med 1993; 35:267-274. (Pubitemid 23084157)
10. Mroz MM, Kreiss K, Lezotte DC, et al. Reexamination of the blood lymphocyte transformation test in the diagnosis of chronic beryllium disease. J Allergy Clin Immunol 1991; 88:54-60.
11. Kreiss K, Newman LS, Mroz MM, Campbell PA. Screening blood test identifies subclinical beryllium disease. J Occup Med 1989; 31:603-608. (Pubitemid 19179743)
12. Kreiss K, Newman LS, Mroz M. Blood testing for chronic beryllium disease. J Occup Med 1991; 33:1188-1189.
13. Stange AW, Furman FJ, Hilmas DE. The beryllium lymphocyte proliferation test: relevant issues in beryllium health surveillance. Am J Ind Med 2004; 46:453-462. (Pubitemid 39507658)
14. Middleton DC, Fink J, Kowalski PJ, et al. Optimizing BeLPT criteria for beryllium sensitization. Am J Ind Med 2008; 51:166-172. (Pubitemid 351272940)
15. Middleton DC, Lewin MD, Kowalski PJ, et al. The BeLPT: algorithms and implications. Am J Ind Med 2006; 49:36-44. (Pubitemid 43083296)
16. Middleton DC, Mayer AS, Lewin MD, et al. Interpreting borderline BeLPT results. Am J Ind Med 2011; 54:205-209. On the basis of current testing algorthims, workers undergoing surveillance BeLPT, this study demonstrated the value of borderline BeLPT results in confirming BeS. At 2% prevalence, posttest probabilities for three-result combinations including borderline tests ranged from 72 to 100%, with the likelihood of increasing as prevalence increases. This suggests that borderline results truly do have value in diagnosing BeS and potentially CBD.
17. Newman LS, Mroz MM, Balkissoon R, Maier LA. Beryllium sensitization progresses to chronic beryllium disease: a longitudinal study of disease risk. Am J Respir Crit Care Med 2005; 171:54-60. (Pubitemid 40051695)
18. Mroz MM, Maier LA, Strand M, et al. Beryllium lymphocyte proliferation test surveillance identifies clinically significant beryllium disease. Am J Ind Med 2009; 52:762-773. This study evaluated all patients who were found to have CBD upon clinical evaluation at National Jewish Health after referral following positive workplace surveillance BeLPT. They found that 19.3% of CBD cases required use of immunosuppressive therapy at an average of 1.4 years after initial diagnosis, and that they had significantly lower resting and exercise arterial oxygen content and higher A-a gradient than did BeS patients. This study supports that CBD detected via initial workplace BeLPT surveillance identifies workers with clinically significant disease.
19. Duggal M, Deubner DC, Curtis AM, Cullen MR. Long-term follow-up of beryllium sensitized workers from a single employer. BMC Public Health 2010; 10:5. This study challenged the hypothesis that CBD detected via workplace surveillance using LPT is not severe. They found that workers with positive BeLPT had significantly lower diffusion capacity by 17.4% of predicted on pulmonary function testing. One third of those found to have CBD at initial examination developed clinical findings suggestive of CBD by the time of follow-up. This tends to suggest that workers identified as having BeS and CBD on workplace surveillance do indeed have clinically relevant disease.
20. Thomas CA, Bailey RL, Kent MS, et al. Efficacy of a program to prevent beryllium sensitization among new employees at a copper-beryllium alloy processing facility. Public Health Rep 2009; 124 (Suppl 1):112-124. A multidisciplinary exposure control program was instituted at a beryllium processing facility that included enhanced engineering and administrative controls, including more frequent BeLPT testing. Despite most exposures being below the OSHA exposure limit, use of more frequent BeLPT surveillance was an important factor in reducing the number of BeS cases detected, demonstrating the utility of the BeLPT as part of a disease prevention program.
21. Cummings KJ, Stefaniak AB, Virji MA, Kreiss K. A reconsideration of acute beryllium disease. Environ Health Perspect 2009; 117:1250-1256.
22. Bailey RL, Thomas CA, Deubner DC, et al. Evaluation of a preventive program to reduce sensitization at a beryllium metal, oxide, and alloy production plant. J Occup Environ Med 2010; 52:505-512.
23. Mikulski MA, Leonard SA, Sanderson WT, et al. Risk of beryllium sensitization in a low-exposed former nuclear weapons cohort from the Cold War era. Am J Ind Med 2011; 54:194-204. The Mikulski et al. study evaluated populations of beryllium-exposed workers from a nuclear weapons facility in operation during the Cold War. The only exposures sustained would have been in the machining or grinding in refinishing of 2% beryllium copper-beryllium parts, a work practice wherein exposures were thought to be low. BeLPT was useful in identifying cases of BeS in this population wherein risk of BeS and CBD was thought low, as no pure beryllium processing occurred there.
24. Mikulski MA, Sanderson WT, Leonard SA, et al. Prevalence of beryllium sensitization among Department of Defense conventional munitions workers at low risk for exposure. J Occup Environ Med 2011; 53:258-265. The Mikulski et al. study evaluated populations of beryllium-exposed workers from a nuclear weapons facility in operation during the Cold War. The only exposures sustained would have been in the machining or grinding in refinishing of 2% beryllium copper-beryllium parts, a work practice wherein exposures were thought to be low. BeLPT was useful in identifying cases of BeS in this population in which risk of BeS and CBD was thought low, as no pure beryllium processing occurred there.
25. Nilsen AM, Vik R, Behrens C, et al. Beryllium sensitivity among workers at a Norwegian aluminum smelter. Am J Ind Med 2010; 53:724-732. Cases of BeS were identified via use of BeLPT among workers at an aluminum smelter, wherein the only exposure to beryllium occurred through trace levels of beryllium present in aluminum. BeLPT may be helpful even in environments not traditionally thought to be at risk for beryllium exposure.
26. Arjomandi M, Seward J, Gotway MB, et al. Low prevalence of chronic beryllium disease among workers at a nuclear weapons research and development facility. J Occup Environ Med 2010; 52:647-652. This study found similar prevalence of BeS at Lawrence Livermore National Laboratory as at Rocky Flats nuclear weapons production facility, despite the exposure levels at the former being significantly lower than those at the latter. Prevalence of CBD, however, was much lower at Lawrence Livermore National Laboratory. This study calls into question whether an exposure-response gradient or threshold exposure level may be present for CBD, but not for BeS.
27. Richeldi L, Kreiss K, Mroz MM, et al. Interaction of genetic and exposure factors in the prevalence of berylliosis. Am J Ind Med 1997; 32:337-340. (Pubitemid 27330274)
28. Richeldi L, Sorrentino R, Saltini C. HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science 1993; 262:242-244. (Pubitemid 23344468)
29. Saltini C, Richeldi L, Losi M, et al. Major histocompatibility locus genetic markers of beryllium sensitization and disease. Eur Respir J 2001; 18:677-684.
30. Wang Z, Farris GM, Newman LS, et al. Beryllium sensitivity is linked to HLADP genotype. Toxicology 2001; 165:27-38. (Pubitemid 32718695)
31. Wang Z, White PS, Petrovic M, et al. Differential susceptibilities to chronic beryllium disease contributed by different Glu69 HLA-DPB1 and -DPA1 alleles. J Immunol 1999; 163:1647-1653. (Pubitemid 29352790)
32. Rossman MD, Stubbs J, Lee CW, et al. Human leukocyte antigen Class II amino acid epitopes: susceptibility and progression markers for beryllium hypersensitivity. Am J Respir Crit Care Med 2002; 165:788-794. (Pubitemid 34229648)
33. Maier LA, McGrath DS, Sato H, et al. Influence ofMHCclass II in susceptibility to beryllium sensitization and chronic beryllium disease. J Immunol 2003; 171:6910-6918. (Pubitemid 37532127)
34. McCanlies EC, Ensey JS, Schuler CR, et al. The association between HLA-DPB1Glu69 and chronic beryllium disease and beryllium sensitization. Am J Ind Med 2004; 46:95-103. (Pubitemid 39062615)
35. Snyder JA, Demchuk E, McCanlies EC, et al. Impact of negatively charged patches on the surface of MHC class II antigen-presenting proteins on risk of chronic beryllium disease. J R Soc Interface 2008; 5:749-758. (Pubitemid 351882141)
36. Gaede KI, Amicosante M, Schurmann M, et al. Function associated transforming growth factor-beta gene polymorphism in chronic beryllium disease. J Mol Med (Berl) 2005; 83:397-405. (Pubitemid 41201804)
37. Snyder JA, Weston A, Tinkle SS, Demchuk E. Electrostatic potential on human leukocyte antigen: implications for putative mechanism of chronic beryllium disease. Environ Health Perspect 2003; 111:1827-1834. (Pubitemid 37526963)
38. Van Dyke MV, Martyny JW, Mroz MM, et al. Risk of chronic beryllium disease by HLA-DPB1 E69 genotype and beryllium exposure in nuclear workers. Am J Respir Crit Care Med 2011; 183:1680-1688. This study found two key findings. First, there was a exposure-response gradient seen for CBD using quantitative beryllium exposure data. Second, there was also an independent effect of genetic variants at the E69 allele increasing risk for both BeS and CBD, with no significant gene-by-environment interaction. This is a key finding given previous work suggesting that risk for CBD likely is mediated by geneby- environment interactions.
39. Dobis DR, Sawyer RT, Gillespie MM, et al. Sulfasalazine and mesalamine modulate beryllium-specific lymphocyte proliferation and inflammatory cytokine production. Am J Respir Cell Mol Biol 2010; 43:458-464. This is the first study to use the BeLPT as a tool to assess new medical treatments for CBD. Mesalamine and sulfasalzine were able to diminish lymphocyte proliferation in stimulated cells, suggesting a potential role for treatment.
40. Fireman E, Mazor O, Kramer M, et al. Noninvasive diagnosis of chronic beryllium disease in workers exposed to hazardous dust in Israel. Occup Environ Med 2010; 67:631-635. Although current algorithms for diagnosis of CBD depend on semi-invasive techniques such as bronchoscopy, this study demonstrated that induced sputum CD4/CD8 cell ratio coupled with peripheral blood BeLPT could diagnose CBD with high sensitivity and specificity.
41. Martin AK, Mack DG, Falta MT, et al. Beryllium-specific CD4(+) T cells in blood as a biomarker of disease progression. J Allergy Clin Immunol 2011; 128:1100-1106; e5. Compared with BeLPT, use of an IFN-g ELISPOT on blood from workers of a beryllium-machining facility identified more cases of sensitization, and was useful in distinguishing those who would go on to develop CBD compared with nonprogressors. This study identifies a potential new avenue for testing for BeS and CBD that may have signficiant technical and safety advantages compared with the BeLPT.
42. Martins LE, Duarte AJ, Aoki V, et al. Lymphocyte proliferation testing in chromium allergic contact dermatitis. Clin Exp Dermatol 2008; 33:472-477. Various concentrations and formulations of chromium were studied to define optimal conditions to perform chromium LPT. With further work, chromium LPT could become a useful tool in occupational surveillance.
43. Lindemann M, Rietschel F, Zabel M, Grosse-Wilde H. Detection of chromium allergy by cellular in vitro methods. Clin Exp Allergy 2008; 38:1468-1475. Sensitivity to chromium detected as total counts per minute on LPT was higher in individuals with chromium allergy and positive patch tests compared with controls, but not when expressed as stimulation index. This study correlated positive patch tests results to LPT and to IFN-g ELISPOT in diagnosing chromium allergy. Further methodologic development is likely needed before chromium LPT may be preferred to patch testing to diagnose chromium allergy.
44. Frigerio E, Pigatto PD, Guzzi G, Altomare G. Metal sensitivity in patients with orthopaedic implants: a prospective study. Contact Dermatitis 2011; 64:273-279. These authors found that subjective history of 'allergy' to a specific metal did not correlate with patch test findings, thus suggesting that some objective measure of sensitization prior to placement of metal orthopedic implants is superior to clinical history. However, this study could not provide substantial evidence to suggest whether LPT could be superior to patch testing.
45. Kwon YM, Thomas P, Summer B, et al. Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 2010; 28:444-450. Interesting study exploring the issue of metal hypersensitivity as a mechanism for the development of pseudotumors in patients with metal-on-metal hip implants. Patients with pseudotumors had positive LPTs to nickel, but not to cobalt or chromium, all of which were present in the implants. Notably, serum ion concentrations of the metals, surrogates for joint loosening via wear and tear, were inversely proportional to LPT positivity. This is a key study in exploring relationships between orthopedic implant failure and underlying immunologic pathophysiologic mechanism.
46. Revell PA. The combined role of wear particles, macrophages and lymphocytes in the loosening of total joint prostheses. J R Soc Interface 2008; 5:1263-1278.
47. Summer B, Paul C, Mazoochian F, et al. Nickel (Ni) allergic patients with complications to Ni containing joint replacement show preferential IL-17 type reactivity to Ni. Contact Dermatitis 2010; 63:15-22. This study found positive nickel LPTs and higher levels of IFN-γ in patients with failing orthopedic implants, but no responses to cobalt. This study supports the concept of sensitization to nickel as a potential pathogenic mechanism leading to early implant failure, and demonstrates utility of LPT in diagnosis.
48. Javed F, Al-Hezaimi K, Almas K, Romanos GE. Is titanium sensitivity associated with allergic reactions in patients with dental implants? A Systematic Review. Clin Implant Dent Relat Res 2011. doi: 10:1111/j.1708- 8208.2010.00330.x. [Epub ahead of print]
49. Egusa H, Ko N, Shimazu T, Yatani H. Suspected association of an allergic reaction with titanium dental implants: a clinical report. J Prosthet Dent 2008; 100:344-347.
50. Kanazawa R, Sato S, Iwamoto N, Teramoto A. Allergic reaction following arachnoid plasty with a fibrin sealant. Neurol Med Chir (Tokyo) 2010; 50:608-610.
51. Toledo F, Silvestre JF, Cuesta L, et al. Contact allergy to beryllium chloride: report of 12 cases. Contact Dermatitis 2011; 64:104-109.
52. Bray PG. Epoxy resins. Occup Med 1999; 14:743-758.
53. Scherpereel A, Tillie-Leblond I, Pommier de Santi P, Tonnel AB. Exposure to methyl methacrylate and hypersensitivity pneumonitis in dental technicians. Allergy 2004; 59:890-892.
54. Hines SE, Barker L, Nagabhushanam V, et al. Respiratory symptoms, spirometry and immunologic sensitivity in epoxy resin workers. Am J Respir Crit Care Med 2011; 183:A1179.
55. Anderson SE, Brown KK, Butterworth LF, et al. Evaluation of irritancy and sensitization potential of metalworking fluid mixtures and components. J Immunotoxicol 2009; 6:19-29. Current thinking behind the cause of hypersensitivity pneumonitis from metalworking fluids is related to microbial contamination of the fluids; however, this study suggests that the metalworking fluids themselves have sensitization potential. Use of the LPT in medical surveillance of workers exposed to metalworking fluids may be of benefit.
56. Sokol WN. Nine episodes of anaphylaxis following cystoscopy caused by Cidex OPA (ortho-phthalaldehyde) high-level disinfectant in 4 patients after cytoscopy. J Allergy Clin Immunol 2004; 114:392-397. (Pubitemid 39119043)
57. Johnson VJ, Reynolds JS, Wang W, et al. Inhalation of ortho-phthalaldehyde vapor causes respiratory sensitization in mice. J Allergy (Cairo) 2011; 2011:751052. After demonstrating sensitization potential of this glutaraldehyde replacement via LLNA, NIOSH researchers demonstrated potential for respiratory sensitization in mice following inhalational challenge. Use of the LPT in medical surveillance of workers exposed to ortho-phthalaldehyde may be of benefit.
58. National Toxicology Program. Chemical information profile for 1-chloro-4- (trifluoromethyl)benzene. Research Triangle Park, North Carolina, USA: National Institute of Environmental Health Sciences; 2009.
59. Maul JJ, Ostrowski PJ, Ublacker GA, et al. Benzotrifluoride and derivatives: useful solvents for organic synthesis and fluorous synthesis. Top Curr Chem 1999; 206:79-105.
60. Franko J, Jackson LG, Meade BJ, Anderson SE. Allergic potential and immunotoxicity induced by topical application of 1-chloro-4-(trifluoromethyl)- benzene (PCBTF) in a murine model. J Allergy (Cairo) 2011; 2011:238513. Both lymphocyte proliferation via LLNA and IFN-γ production in mice exposed to the chemical PCBTF suggest that the agent is a sensitizer. PCBTF is used in many different industrial applications, therefore yielding many opportunities for occupational exposure, wherein LPT may be of benefit via surveillance.
61. Milovanova TN, Popma SH, Cherian S, et al. Flow cytometric test for beryllium sensitivity. Cytometry B Clin Cytom 2004; 60:23-30. (Pubitemid 38880152)
62. Anderson SE, Brown KK, Butterworth LF, et al. Evaluation of irritancy and sensitization potential of metalworking fluid mixtures and components. J Immunotoxicol 2009; 6:19-29. [55]
63. Anderson SE, Umbright C, Sellamuthu R, et al. Irritancy and allergic responses induced by topical application of orthophthalaldehyde. Toxicol Sci 2010; 115:435-443. [06]
64. Arjomandi M, Seward J, Gotway MB, et al. Low prevalence of chronic beryllium disease among workers at a nuclear weapons research and development facility. J Occup Environ Med 2010; 52:647-652. [26]
65. Dobis DR, Sawyer RT, Gillespie MM, et al. Sulfasalazine and mesalamine modulate beryllium-specific lymphocyte proliferation and inflammatory cytokine production. Am J Respir Cell Mol Biol 2010; 43:458-464. [39]
66. Duggal M, Deubner DC, Curtis AM, Cullen MR. Long-term follow-up of beryllium sensitized workers from a single employer. BMC Public Health 2010; 10:5. [19]
67. Fireman E, Mazor O, Kramer M, et al. Noninvasive diagnosis of chronic beryllium disease in workers exposed to hazardous dust in Israel. Occup Environ Med 2010; 67:631-635. [40]
68. Franko J, Jackson LG, Meade BJ, Anderson SE. Allergic potential and immunotoxicity induced by topical application of 1-chloro-4-(trifluoromethyl) benzene (PCBTF) in a murine model. J Allergy (Cairo) 2011; 2011:238513. [60]
69. Frigerio E, Pigatto PD, Guzzi G, Altomare G. Metal sensitivity in patients with orthopaedic implants: a prospective study. Contact Dermatitis 2011; 64:273-279. [44]
70. Heffler E, Nebiolo F, Asero R, Guida G, et al. Clinical manifestations, co-sensitizations, and immunoblotting profiles of buckwheat-allergic patients. Allergy 2011; 66:264-270.
71. Johnson VJ, Reynolds JS, Wang W, et al. Inhalation of ortho-phthalaldehyde vapor causes respiratory sensitization in mice. J Allergy (Cairo) 2011; 2011:751052. [57]
72. Krop EJM, Doekes G, Heederik DJJ, Aalberse RC, et al. IgG4 antibodies against rodents in laboratory animal workers do not protect against allergic sensitization. Allergy 2011; 66:517-522.
73. Kwon YM, Thomas P, Summer B, et al. Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 2010; 28:444-450. [45]
74. Lindemann M, Rietschel F, Zabel M, Grosse-Wilde H. Detection of chromium allergy by cellular in vitro methods. Clin Exp Allergy 2008; 38:1468-1475. [43]
75. Martin AK, Mack DG, Falta MT, et al. Beryllium-specific CD4(+) T cells in blood as a biomarker of disease progression. J Allergy Clin Immunol 2011; 128:1100-1106. e5 [41]
76. Martins LE, Duarte AJ, Aoki V, et al. Lymphocyte proliferation testing in chromium allergic contact dermatitis. Clin Exp Dermatol 33:472-477. [42]
77. Middleton DC, Mayer AS, Lewin MD, et al. Interpreting borderline BeLPT results. Am J Ind Med 2011; 54:205-209. [16]
78. Mikulski MA, Leonard SA, Sanderson WT, et al. Risk of beryllium sensitization in a low-exposed former nuclear weapons cohort from the Cold War era. Am J Ind Med 2011; 54:194-204. [23]
79. Mikulski MA, Sanderson WT, Leonard SA, et al. Prevalence of beryllium sensitization among Department of Defense conventional munitions workers at low risk for exposure. J Occup Environ Med 2011; 53:258-265. [24]
80. Moscato G, Pala G, Boillat MA, Folletti I, et al. EAACI Position Paper: Prevention of work-related respiratory allergies among pre-apprentices or apprentices and young workers. Allergy 2011; 66:1164-1173.
81. Mroz MM, Maier LA, Strand M, et al. Beryllium lymphocyte proliferation test surveillance identifies clinically significant beryllium disease. Am J Ind Med 2009; 52:762-773. [18]
82. Ni CY, Dou X, Chen JY, Zhu XJ, et al. Contact Sensitization in Chinese Patients with Hand Eczema. Dermatitis 2011; 22:211-215.
83. Nilsen AM,Vik R, Behrens C, et al. Beryllium sensitivity among workers at a Norwegian aluminum smelter. Am J Ind Med 2010; 53:724-732. [25]
84. Robst J, Van Gilder J. The role of childhood sexual victimization in the occupational choice of adults. Appl Econ 2011; 43:341-354.
85. Roederer M. Interpretation of Cellular Proliferation Data: Avoid the Panglossian. Cytom Part A 2011; 79A:95-101, 2011 Feb..
86. Sang KJC, Gyi DE, Haslam CO. Stakeholder perspectives on managing the occupational health of UK business drivers: A qualitative approach. Appl Ergon 2011; 42:419-425.
87. Summer B, Paul C, Mazoochian F, et al. Nickel (Ni) allergic patients with complications to Ni containing joint replacement show preferential IL-17 type reactivity to Ni. Contact Dermatitis 2010; 63:15-22. [47]
88. Thomas CA, Bailey RL, KentMS, et al. Efficacy of a program to prevent beryllium sensitization among new employees at a copper-beryllium alloy processing facility. Public Health Rep 124(Suppl 1)2009:112-124. [20]
89. Van Dyke MV, Martyny JW, Mroz MM, et al. Risk of chronic beryllium disease by HLA-DPB1 E69 genotype and beryllium exposure in nuclear workers. Am J Respir Crit Care Med 2011; 183:1680-1688. [38]
90. van Wijk RG, Patiwael JA, de Jong NW, de Groot H, et al. Occupational rhinitis in bell pepper greenhouse workers: determinants of leaving work and the effects of subsequent allergen avoidance on health-related quality of life. Allergy 2011; 66:903-908.
91. Wan L, Zhu SY, Li YY, Liu S, et al. Production and characterization of LEA29Y, a variant of cytotoxic T-lymphocyte antigen 4-immunoglobulin, in Pichia pastoris. Appl Microbiol Biotechnol 2011; 91:543-551.