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Primary Immunodeficiency Presentations And 10 Warning Signs
Abstracts AB157
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
591
593
592
594
Primary Immunodeficiency Presentations And 10 Warning Signs M. L. Tierce, IV, E. Secord; Wayne State University/Children’s Hospital of Michigan, Detroit, MI. RATIONALE: Several have published clinical experiences, approaches to the patient, and reasons to consider primary immune deficiency (PID) diagnoses. One widely distributed resource, 10 Warning Signs of Primary Immunodeficiency, has been questioned recently as to its evidence basis and clinical application. METHODS: A retrospective chart review of primary immunodeficiency patients was conducted. Of the 144 initial consultation histories reviewed, those with a resulting PID diagnosis were included in the analysis. The initial presentation data was summarized and then expressed using the 10 Warning Signs as a framework to characterize patients with PID. RESULTS: 12 of 13 patients with DiGeorge presented with cardiac defects, the other with low T cell counts. Agammaglobulinemia presented with infection, some consanguinity, and unexpectedly 2 of 5 with opportunistic infections. CGD patients had Aspergillus and/or Staphylococcus infections. 7 of 11 CVID patients had autoimmune disease as presenting first illness. Hypogammaglobulinemia and specific antibody deficiency primarily had sinopulmonary disease. IL-12/IFN gamma pathway deficiency presented with atypical Mycobacterium infection. One patient had dental abscesses and NK cell deficiency. SCID patients presented with opportunistic infections or a previous sibling diagnosis, and the selective IgA patients had sinopulmonary and GI complaints. Of 61 patients with a PID diagnosis, roughly one third had 2 or more of the 10 Warning Signs and another third had none. CONCLUSIONS: While resources like 10 Warning Signs increase awareness of PID, for timely referral and diagnosis practitioners should maintain a high index of suspicion and be aware of classic PID presentations and associations.
Prevalence of Malignancies in Various Primary Immune Deficiency States: A systematic review D. M. George-Grandon, K. Osann, S. Gupta; UCI, Irvine, CA. RATIONAL: Patients with primary immunodeficiencies (PID) are at risk for neoplastic complications which remain the second most common cause of mortality. We conducted a systematic review to determine the weighted prevalence of malignancies in various PID populations. METHODS: PUBMED and MEDLINE databases were searched for articles about malignancies in various PIDs. The PIDs were searched based on the International Union of Immunological Societies classification and articles from 1970-2011 were retrieved. Articles were reviewed with predetermined criteria before they were included in the review. Around 200 articles with data on malignancies in the various PIDs were reviewed of which around 28 met all inclusion criteria. RESULTS: Among individuals presenting with the various PIDs, the weighted prevalence of malignancies were highest in Ataxia Telangiectasia (AT) with 1500/10,000, Hyper ImmunoglobulinE (Hyper IgE) syndrome at 1100/10,000, Wiskott Aldrcih Syndrome (WAS) at 968/ 10,000, Common Variable Immune Deficiency (CVID) at 700/10,000 and lower prevalence in Hyper ImmunoglobulinM syndrome, X-Linked Agammaglobulinemia (XLA), ImmunoglobulinG&ImmunoglobulingA subclass deficiency and Di George at 400/10,000, 300/10,000, 100/ 10,000 and 80/10,000 respectively. Among the malignancies reported, there was a high prevalence of lymphomas seen among AT and WAS populations where the weighted prevalence was 900/10,000 and 800/ 10,000 respectively, in CVID 320/10,000 followed by stomach and breast cancer at 100/10,000 and 60/10,000 respectively. CONCLUSIONS: Prevalence rates of malignancies vary among the different type of PIDs with a higher prevalence seen with DNA repair defects and antibody deficiencies. Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing with the goal of earlier detection and treatment .
Phenotypic Comparison of B cells in Discordant Identical Twins with Common Variable Immunodeficiency and Recurrent Sino-Pulmonary Infection Patients T. A. Hwangpo, E. Szymanska, C. R. Liu, M. G. Brand, E. E. Brown, H. Schroeder; University of Alabama at Birmingham, Birmingham, AL, AL. RATIONALE: In our Adult Primary Immunodeficiency Clinic in the Southeastern United States, we observed that nearly half of our patients with Common Variable Immune Deficiency (CVID) and half of our patients with recurrent sinopulmonary infections with normal serum immunoglobulins (RESPI) inherit HLA*B44. Recent studies by others suggest that clinical symptoms in CVID can correlate with a reduction in the memory B cell compartment. To test this hypothesis, we evaluated serial B cell numbers over time in a set of identical HLA*B44+ twins discordant for CVID and RESPI. METHODS: Whole blood was collected at a minimum of seven time points over a 14 month period. Plasma cells, memory B cells, immature B cells, transitional B cells, and mature B cells were isolated from whole blood and counted via FACS. One-way ANOVA and 2-sample test were used to analyze the means of these cells. RESULTS: Memory IgD+ and memory IgD- cells were significantly lower in the CVID twin (mean 3.2X105 in CVID, 1.0X106 in RESPI, p <0.012; mean 2.4X105 in CVID, 8.2X105 in RESPI, p <0.017, respectively). There was a trend for higher immature B cells and lower transitional B cells in the CVID twin compared to the RESPI twin although this did not reach statistical significance. CONCLUSIONS: The twin with CVID appears to have fewer memory B cells, fewer transitional cells, and more immature B cells than her RESPI twin sister. Defects in either B cell maturation signaling or memory B cell generation may be contributing to the discordant phenotype.
MONDAY
Primary Immunodeficiency in Microcephalic Osteodysplastic Primordial Dwarfism Type I/III (MOPD I/III) M. L. DeFelice, M. B. Bober, C. C. Chang, S. J. McGeady; Thomas Jefferson University/Alfred I. duPont Hospital for Children, Wilmington, DE. RATIONALE: MOPD I/III is a rare autosomal recessive disorder caused by mutations in the U4atac gene. There have been approximately 30 reported cases with most patients having lifespans of only 1-2 years. Limited data shows these children frequently succumb to serious bacterial infection, however immunodeficiency associated with this syndrome has never been reported. METHODS: Two children with MOPD I/III were evaluated for possible immune dysregulation. RESULTS: A 3yo female referred for evaluation after EGD/colonoscopy revealed a paucity of plasma cells was found to have IgG 127 mg/dL, IgA 10 mg/dL, IgM 39 mg/dL, CD195265 cells/mcL (normal 390-1400), CD451509 cells/mcL (normal 700-2200), CD85317 cells/mcL (normal 490-1300), adequate response to tetanus and diphtheria vaccination, and failure to respond to polysaccharide antigens. She started immunoglobulin replacement therapy at age 2 years and has required only 4 courses of antibiotics. A 9 month old female with a history of sepsis was found to have IgG 252 mg/dL, IgA 7 mg/dL, IgM 43 mg/dL, CD195390 cells/mcL (normal 610-2600), CD451074 cells/mcL (normal 1400-4300), CD85197 cells/mcL (normal 500-1700), adequate response to tetanus and diphtheria vaccination, and poor response to prevnar. CONCLUSIONS: Primary immunodeficiency is a possible reason for increased morbidity and mortality in patients with MOPD I/III. Immunoglobulin replacement therapy may prolong the lives of children with this syndrome and associated hypogammaglobulinemia and failure to respond to polysaccharide antigens. To date, this is the first report of immunodeficiency in patients with MOPD I/III. Evaluation and appropriate treatment for immunodeficiency may drastically improve survival and quality of life for these patients.
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
591
593
592
594
Primary Immunodeficiency Presentations And 10 Warning Signs M. L. Tierce, IV, E. Secord; Wayne State University/Children’s Hospital of Michigan, Detroit, MI. RATIONALE: Several have published clinical experiences, approaches to the patient, and reasons to consider primary immune deficiency (PID) diagnoses. One widely distributed resource, 10 Warning Signs of Primary Immunodeficiency, has been questioned recently as to its evidence basis and clinical application. METHODS: A retrospective chart review of primary immunodeficiency patients was conducted. Of the 144 initial consultation histories reviewed, those with a resulting PID diagnosis were included in the analysis. The initial presentation data was summarized and then expressed using the 10 Warning Signs as a framework to characterize patients with PID. RESULTS: 12 of 13 patients with DiGeorge presented with cardiac defects, the other with low T cell counts. Agammaglobulinemia presented with infection, some consanguinity, and unexpectedly 2 of 5 with opportunistic infections. CGD patients had Aspergillus and/or Staphylococcus infections. 7 of 11 CVID patients had autoimmune disease as presenting first illness. Hypogammaglobulinemia and specific antibody deficiency primarily had sinopulmonary disease. IL-12/IFN gamma pathway deficiency presented with atypical Mycobacterium infection. One patient had dental abscesses and NK cell deficiency. SCID patients presented with opportunistic infections or a previous sibling diagnosis, and the selective IgA patients had sinopulmonary and GI complaints. Of 61 patients with a PID diagnosis, roughly one third had 2 or more of the 10 Warning Signs and another third had none. CONCLUSIONS: While resources like 10 Warning Signs increase awareness of PID, for timely referral and diagnosis practitioners should maintain a high index of suspicion and be aware of classic PID presentations and associations.
Prevalence of Malignancies in Various Primary Immune Deficiency States: A systematic review D. M. George-Grandon, K. Osann, S. Gupta; UCI, Irvine, CA. RATIONAL: Patients with primary immunodeficiencies (PID) are at risk for neoplastic complications which remain the second most common cause of mortality. We conducted a systematic review to determine the weighted prevalence of malignancies in various PID populations. METHODS: PUBMED and MEDLINE databases were searched for articles about malignancies in various PIDs. The PIDs were searched based on the International Union of Immunological Societies classification and articles from 1970-2011 were retrieved. Articles were reviewed with predetermined criteria before they were included in the review. Around 200 articles with data on malignancies in the various PIDs were reviewed of which around 28 met all inclusion criteria. RESULTS: Among individuals presenting with the various PIDs, the weighted prevalence of malignancies were highest in Ataxia Telangiectasia (AT) with 1500/10,000, Hyper ImmunoglobulinE (Hyper IgE) syndrome at 1100/10,000, Wiskott Aldrcih Syndrome (WAS) at 968/ 10,000, Common Variable Immune Deficiency (CVID) at 700/10,000 and lower prevalence in Hyper ImmunoglobulinM syndrome, X-Linked Agammaglobulinemia (XLA), ImmunoglobulinG&ImmunoglobulingA subclass deficiency and Di George at 400/10,000, 300/10,000, 100/ 10,000 and 80/10,000 respectively. Among the malignancies reported, there was a high prevalence of lymphomas seen among AT and WAS populations where the weighted prevalence was 900/10,000 and 800/ 10,000 respectively, in CVID 320/10,000 followed by stomach and breast cancer at 100/10,000 and 60/10,000 respectively. CONCLUSIONS: Prevalence rates of malignancies vary among the different type of PIDs with a higher prevalence seen with DNA repair defects and antibody deficiencies. Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing with the goal of earlier detection and treatment .
Phenotypic Comparison of B cells in Discordant Identical Twins with Common Variable Immunodeficiency and Recurrent Sino-Pulmonary Infection Patients T. A. Hwangpo, E. Szymanska, C. R. Liu, M. G. Brand, E. E. Brown, H. Schroeder; University of Alabama at Birmingham, Birmingham, AL, AL. RATIONALE: In our Adult Primary Immunodeficiency Clinic in the Southeastern United States, we observed that nearly half of our patients with Common Variable Immune Deficiency (CVID) and half of our patients with recurrent sinopulmonary infections with normal serum immunoglobulins (RESPI) inherit HLA*B44. Recent studies by others suggest that clinical symptoms in CVID can correlate with a reduction in the memory B cell compartment. To test this hypothesis, we evaluated serial B cell numbers over time in a set of identical HLA*B44+ twins discordant for CVID and RESPI. METHODS: Whole blood was collected at a minimum of seven time points over a 14 month period. Plasma cells, memory B cells, immature B cells, transitional B cells, and mature B cells were isolated from whole blood and counted via FACS. One-way ANOVA and 2-sample test were used to analyze the means of these cells. RESULTS: Memory IgD+ and memory IgD- cells were significantly lower in the CVID twin (mean 3.2X105 in CVID, 1.0X106 in RESPI, p <0.012; mean 2.4X105 in CVID, 8.2X105 in RESPI, p <0.017, respectively). There was a trend for higher immature B cells and lower transitional B cells in the CVID twin compared to the RESPI twin although this did not reach statistical significance. CONCLUSIONS: The twin with CVID appears to have fewer memory B cells, fewer transitional cells, and more immature B cells than her RESPI twin sister. Defects in either B cell maturation signaling or memory B cell generation may be contributing to the discordant phenotype.
MONDAY
Primary Immunodeficiency in Microcephalic Osteodysplastic Primordial Dwarfism Type I/III (MOPD I/III) M. L. DeFelice, M. B. Bober, C. C. Chang, S. J. McGeady; Thomas Jefferson University/Alfred I. duPont Hospital for Children, Wilmington, DE. RATIONALE: MOPD I/III is a rare autosomal recessive disorder caused by mutations in the U4atac gene. There have been approximately 30 reported cases with most patients having lifespans of only 1-2 years. Limited data shows these children frequently succumb to serious bacterial infection, however immunodeficiency associated with this syndrome has never been reported. METHODS: Two children with MOPD I/III were evaluated for possible immune dysregulation. RESULTS: A 3yo female referred for evaluation after EGD/colonoscopy revealed a paucity of plasma cells was found to have IgG 127 mg/dL, IgA 10 mg/dL, IgM 39 mg/dL, CD195265 cells/mcL (normal 390-1400), CD451509 cells/mcL (normal 700-2200), CD85317 cells/mcL (normal 490-1300), adequate response to tetanus and diphtheria vaccination, and failure to respond to polysaccharide antigens. She started immunoglobulin replacement therapy at age 2 years and has required only 4 courses of antibiotics. A 9 month old female with a history of sepsis was found to have IgG 252 mg/dL, IgA 7 mg/dL, IgM 43 mg/dL, CD195390 cells/mcL (normal 610-2600), CD451074 cells/mcL (normal 1400-4300), CD85197 cells/mcL (normal 500-1700), adequate response to tetanus and diphtheria vaccination, and poor response to prevnar. CONCLUSIONS: Primary immunodeficiency is a possible reason for increased morbidity and mortality in patients with MOPD I/III. Immunoglobulin replacement therapy may prolong the lives of children with this syndrome and associated hypogammaglobulinemia and failure to respond to polysaccharide antigens. To date, this is the first report of immunodeficiency in patients with MOPD I/III. Evaluation and appropriate treatment for immunodeficiency may drastically improve survival and quality of life for these patients.