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Statistical Analysis of Correlates of Pneumococcal Antibody Level and Avidity in Patients with Recurrent Infections
Abstracts AB135
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
511
T-B-NK1 Severe Combined Immunodeficiency (SCID) Identified by Statewide Newborn Screening A. Thomas1, M. W. Baker1, S. M. Yannone2, M. J. Cowan2, J. M. Puck2, R. A. Gatti3, A. R. Byrom1, J. W. Verbsky4, J. M. Routes4, K. B. De Santes1, J. E. Gern1, C. M. Seroogy1; 1University of Wisconsin, Madison, WI, 2University of California- San Francisco, San Francisco, CA, 3University of California- Los Angeles, Los Angeles, CA, 4Medical College of Wisconsin, Milwaukee, WI. RATIONALE: In 2008, the State of Wisconsin began screening for SCID in the routine newborn screen (NBS). SCID typically presents in the first few months of life with life-threatening infections and is fatal without immune reconstitution. Here we report SCID found by newborn screen in a full-term male infant of non-consanginous parents. METHODS: T-cell receptor excision circle (TREC) analysis was performed by QPCR on newborn filter cards. Other analyses included flow cytometry, Western blot, gene sequencing and fibroblast clonogenic survival assay (CSA). RESULTS: The patient’s NBS on DOL 1 revealed low TREC and repeat testing confirmed this result. On DOL 8, he was placed in protective isolation. Physical exam was normal except for absent lymphoid tissue. Initial flow cytometry demonstrated absolute CD3: 111 (2500-5600); CD19: 28 (430-3000); NK: 1112 (170-830) and results were validated two more times before transplant. IgM and IgA levels were below normal and lymphocyte function was severely decreased. These results were consistent with a diagnosis of T-B-NK1 SCID. ADA and PNP enzyme activity were normal. Genetic sequencing for: RAG1/2, ARTEMIS, IL7R, JAK3, LIGIV, IL2RG were normal. Fibroblast CSA demonstrated mild radiosensitvity and normal protein levels for Artemis, DNA-PKcs and Cernunnos. He underwent a matched unrelated umbilical cord blood transplant on DOL 77 and was discharged home on DOL 107 with evidence of myeloid and lymphoid engraftment. CONCLUSIONS: This case of SCID was detected by NBS and validates this approach for early detection. Investigation is ongoing to determine the molecular basis in this case of T-B-NK1 SCID.
CD21-/low B Cells Are Increased in Both Common Variable Immune Deficiency (CVID) and Specific Antibody Deficiency (SAD) A. Elizalde, S. Hudey, M. Dorsey, E. Perez, J. Sleasman, P. Sriaroon; University of South Florida/All Children’s Hospital, St. Petersburg, FL. RATIONALE: CVID and SAD are similar because of increased incidence of recurrent bacterial infections but CVID subjects have a higher risk for autoimmune complications. Increased percentages of CD21-/low B cells reflect B cell activation and have been associated with autoimmunity. We sought to compare B cell sub-populations among patients with CVID with or without autoimmunity, SAD, and healthy individuals. METHODS: Using fresh whole blood samples multiple parameter flow cytometry analysis enumerated CD19/CD27 with extended markers including surface IgM/IgD and CD21 in 37 healthy controls (HC), 31 CVID subjects, and 8 SAD defined as subjects with recurrent infections and decreased antibody response to polysaccharide vaccine. RESULTS: There were no major differences in total CD191 percentages among the groups. As expected CVID subjects had lower CD271 memory B cells percentages compared to HC (14.2 6 13.4% versus 33.0 6 13.62% respectively, p < 0.05, Kruskal-Wallis method). Class switch recombination among CD271 memory B cells was similar in SAD and HC (0.83 6 0.39 versus 0.94 6 0.62)). Surprisingly, CD21-/low B cells are increased in SAD, similar to CVID group (18.20 6 26.35, 10.20 6 12.59 respectively versus 6.70 6 3.37 HC). CONCLUSIONS: Similar to CVID, subjects with SAD have increased CD21-/low B cells but show percentages of class switched memory B cells similar to HC, indicating a distinct B cell phenotype. These findings suggest that B cells are activated in SAD but maturation and class switch recombination is not affected.
512
513
Smoking, Environmental Tobacco Smoke, and Aspirin Exacerbated Respiratory Disease J. E. Chang1, D. Ding2, A. A. White1, J. Martin3, D. D. Stevenson1; 1 Scripps Clinic, San Diego, CA, 2UCSD, San Diego, CA, 3Arquitecto Marcide Hospital, La Coruna, SPAIN. RATIONALE: Environmental tobacco smoke (ETS) has clear links with many conditions, including asthma, lung and sinus cancer, but there is no evidence on ETS with aspirin exacerbated respiratory disease (AERD). This study investigates whether or not active or environmental smoke exposure is associated with developing AERD. METHODS: In a case-control study, 260 AERD patients and their asymptomatic spouses were enrolled from 2003 to 2009. Using multiple logistic regression analysis to adjust for age, sex, and location of childhood residence, data were analyzed for an association between smoking exposure and AERD. RESULTS: Ever-smokers had an odds ratio (OR) of 1.54 (95% CI:1.04, 2.28) for having AERD, compared to never-smokers. For childhood ETS exposure, an OR of 3.46 (95% CI:2.22, 5.39) was found. Among individuals exposed during childhood, a dose-response trend between ETS exposure duration and AERD was discovered. Results also showed individuals were five times more likely to develop AERD (95% CI:2.75, 9.43) if exposed to ETS during both childhood and adulthood. However, no statistically significant association was found between AERD and those exposed only as adults (OR:1.60, 95% CI:0.75-3.40). This suggests that the effect of combined childhood and adulthood ETS may be augmented by prior childhood exposure. CONCLUSIONS: Active smoking and childhood ETS exposure have increased odds for developing AERD. In particular, duration of exposure to ETS as children, as well as combined childhood and adulthood exposure have major effects. This study suggests that ETS is at least one contributor to chronic sinusitis, asthma and nasal polyps in patients with the syndrome of AERD.
SUNDAY
510
Statistical Analysis of Correlates of Pneumococcal Antibody Level and Avidity in Patients with Recurrent Infections A. J. Fried1, M. L. Altrich2, J. F. Halsey2, F. A. Bonilla1; 1Children’s Hospital Boston, Boston, MA, 2Viracor-IBT Laboratories, Lenexa, KS. RATIONALE: We correlated subject characteristics with the levels and avidities of antibodies to 12 pneumococcal serotypes. METHODS: We measured concentration and avidity of antibodies to 12 pneumococcal serotypes in 78 patients aged 0.6-18 years evaluated for recurrent infections, and in 80 individuals evaluated for peanut allergy ages 0.4-15 years. Non-parametric statistics were used to correlate gender, age, serum immunoglobulin levels, and immunization history with responses and to compare patients and ‘‘controls’’. RESULTS: Level and avidity were highly correlated only for two types among patients. There was no consistent correlation of age and level in either group; there was a significant negative correlation of age and avidity for approximately half of the types in both groups. There was inconsistent correlation of total IgG or IgG subclasses with either levels or avidity. Distributions of levels and avidity for each pneumococcal type varied significantly from each other. For serotypes in the conjugate vaccine, there was a general association of avidity (but not level) with the total number of vaccine doses. There was significant association of levels (but not avidity) with vaccination history for the non-conjugate types. There was inconsistent correlation of level and avidity with time from immunization for all types. CONCLUSION: Overall, concentration and avidity correlate independently with immunologic characteristics and exposure history and are markedly different between pneumococcal types.
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
511
T-B-NK1 Severe Combined Immunodeficiency (SCID) Identified by Statewide Newborn Screening A. Thomas1, M. W. Baker1, S. M. Yannone2, M. J. Cowan2, J. M. Puck2, R. A. Gatti3, A. R. Byrom1, J. W. Verbsky4, J. M. Routes4, K. B. De Santes1, J. E. Gern1, C. M. Seroogy1; 1University of Wisconsin, Madison, WI, 2University of California- San Francisco, San Francisco, CA, 3University of California- Los Angeles, Los Angeles, CA, 4Medical College of Wisconsin, Milwaukee, WI. RATIONALE: In 2008, the State of Wisconsin began screening for SCID in the routine newborn screen (NBS). SCID typically presents in the first few months of life with life-threatening infections and is fatal without immune reconstitution. Here we report SCID found by newborn screen in a full-term male infant of non-consanginous parents. METHODS: T-cell receptor excision circle (TREC) analysis was performed by QPCR on newborn filter cards. Other analyses included flow cytometry, Western blot, gene sequencing and fibroblast clonogenic survival assay (CSA). RESULTS: The patient’s NBS on DOL 1 revealed low TREC and repeat testing confirmed this result. On DOL 8, he was placed in protective isolation. Physical exam was normal except for absent lymphoid tissue. Initial flow cytometry demonstrated absolute CD3: 111 (2500-5600); CD19: 28 (430-3000); NK: 1112 (170-830) and results were validated two more times before transplant. IgM and IgA levels were below normal and lymphocyte function was severely decreased. These results were consistent with a diagnosis of T-B-NK1 SCID. ADA and PNP enzyme activity were normal. Genetic sequencing for: RAG1/2, ARTEMIS, IL7R, JAK3, LIGIV, IL2RG were normal. Fibroblast CSA demonstrated mild radiosensitvity and normal protein levels for Artemis, DNA-PKcs and Cernunnos. He underwent a matched unrelated umbilical cord blood transplant on DOL 77 and was discharged home on DOL 107 with evidence of myeloid and lymphoid engraftment. CONCLUSIONS: This case of SCID was detected by NBS and validates this approach for early detection. Investigation is ongoing to determine the molecular basis in this case of T-B-NK1 SCID.
CD21-/low B Cells Are Increased in Both Common Variable Immune Deficiency (CVID) and Specific Antibody Deficiency (SAD) A. Elizalde, S. Hudey, M. Dorsey, E. Perez, J. Sleasman, P. Sriaroon; University of South Florida/All Children’s Hospital, St. Petersburg, FL. RATIONALE: CVID and SAD are similar because of increased incidence of recurrent bacterial infections but CVID subjects have a higher risk for autoimmune complications. Increased percentages of CD21-/low B cells reflect B cell activation and have been associated with autoimmunity. We sought to compare B cell sub-populations among patients with CVID with or without autoimmunity, SAD, and healthy individuals. METHODS: Using fresh whole blood samples multiple parameter flow cytometry analysis enumerated CD19/CD27 with extended markers including surface IgM/IgD and CD21 in 37 healthy controls (HC), 31 CVID subjects, and 8 SAD defined as subjects with recurrent infections and decreased antibody response to polysaccharide vaccine. RESULTS: There were no major differences in total CD191 percentages among the groups. As expected CVID subjects had lower CD271 memory B cells percentages compared to HC (14.2 6 13.4% versus 33.0 6 13.62% respectively, p < 0.05, Kruskal-Wallis method). Class switch recombination among CD271 memory B cells was similar in SAD and HC (0.83 6 0.39 versus 0.94 6 0.62)). Surprisingly, CD21-/low B cells are increased in SAD, similar to CVID group (18.20 6 26.35, 10.20 6 12.59 respectively versus 6.70 6 3.37 HC). CONCLUSIONS: Similar to CVID, subjects with SAD have increased CD21-/low B cells but show percentages of class switched memory B cells similar to HC, indicating a distinct B cell phenotype. These findings suggest that B cells are activated in SAD but maturation and class switch recombination is not affected.
512
513
Smoking, Environmental Tobacco Smoke, and Aspirin Exacerbated Respiratory Disease J. E. Chang1, D. Ding2, A. A. White1, J. Martin3, D. D. Stevenson1; 1 Scripps Clinic, San Diego, CA, 2UCSD, San Diego, CA, 3Arquitecto Marcide Hospital, La Coruna, SPAIN. RATIONALE: Environmental tobacco smoke (ETS) has clear links with many conditions, including asthma, lung and sinus cancer, but there is no evidence on ETS with aspirin exacerbated respiratory disease (AERD). This study investigates whether or not active or environmental smoke exposure is associated with developing AERD. METHODS: In a case-control study, 260 AERD patients and their asymptomatic spouses were enrolled from 2003 to 2009. Using multiple logistic regression analysis to adjust for age, sex, and location of childhood residence, data were analyzed for an association between smoking exposure and AERD. RESULTS: Ever-smokers had an odds ratio (OR) of 1.54 (95% CI:1.04, 2.28) for having AERD, compared to never-smokers. For childhood ETS exposure, an OR of 3.46 (95% CI:2.22, 5.39) was found. Among individuals exposed during childhood, a dose-response trend between ETS exposure duration and AERD was discovered. Results also showed individuals were five times more likely to develop AERD (95% CI:2.75, 9.43) if exposed to ETS during both childhood and adulthood. However, no statistically significant association was found between AERD and those exposed only as adults (OR:1.60, 95% CI:0.75-3.40). This suggests that the effect of combined childhood and adulthood ETS may be augmented by prior childhood exposure. CONCLUSIONS: Active smoking and childhood ETS exposure have increased odds for developing AERD. In particular, duration of exposure to ETS as children, as well as combined childhood and adulthood exposure have major effects. This study suggests that ETS is at least one contributor to chronic sinusitis, asthma and nasal polyps in patients with the syndrome of AERD.
SUNDAY
510
Statistical Analysis of Correlates of Pneumococcal Antibody Level and Avidity in Patients with Recurrent Infections A. J. Fried1, M. L. Altrich2, J. F. Halsey2, F. A. Bonilla1; 1Children’s Hospital Boston, Boston, MA, 2Viracor-IBT Laboratories, Lenexa, KS. RATIONALE: We correlated subject characteristics with the levels and avidities of antibodies to 12 pneumococcal serotypes. METHODS: We measured concentration and avidity of antibodies to 12 pneumococcal serotypes in 78 patients aged 0.6-18 years evaluated for recurrent infections, and in 80 individuals evaluated for peanut allergy ages 0.4-15 years. Non-parametric statistics were used to correlate gender, age, serum immunoglobulin levels, and immunization history with responses and to compare patients and ‘‘controls’’. RESULTS: Level and avidity were highly correlated only for two types among patients. There was no consistent correlation of age and level in either group; there was a significant negative correlation of age and avidity for approximately half of the types in both groups. There was inconsistent correlation of total IgG or IgG subclasses with either levels or avidity. Distributions of levels and avidity for each pneumococcal type varied significantly from each other. For serotypes in the conjugate vaccine, there was a general association of avidity (but not level) with the total number of vaccine doses. There was significant association of levels (but not avidity) with vaccination history for the non-conjugate types. There was inconsistent correlation of level and avidity with time from immunization for all types. CONCLUSION: Overall, concentration and avidity correlate independently with immunologic characteristics and exposure history and are markedly different between pneumococcal types.