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Concomitant FMF and TRAPS Mutation In a Periodic Fever Patient
AB184 Abstracts
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
633
The Immunoglobulin Diagnosis, Evaluation, and Key Learnings (IDEaL) Patient Registry: Analysis Of Ig Dosing, Infection Control, and Quality-Of-Life Assessments In Our Primary Immunodeficiency Population Sean Kearns, PhD1, Keith Crawford1, Loretta Kristofek, RN1, Robbyn Kirylo1, Dr. Luqman Seidu, MD2; 1Coram Clinical Trials, Denver, CO, 2 Allergy and Asthma of Atlanta, LLC, Atlanta, GA. RATIONALE: The IDEaL Patient Registry collects longitudinal information on patients receiving immunoglobulin (Ig) replacement therapy from Coram Specialty Infusion Services in an alternate care setting. This poster is focused on Ig dosing, infection control, and quality-of-life assessments in the primary immune deficiency (PID) population. METHODS: Patients of our 138 investigators are eligible for the Registry. With patient consent acquired, patient information from July 2010 onward that had been collected by Coram providers was entered into the IDEaL database. Additionally, patients were asked to complete an SF-36 questionnaire and an LQIQ survey every six months. RESULTS: As of August 2013, 235 PID patients were enrolled. The average dose for SCIg was 135 mg/kg per week, and for IVIg, 409 mg/kg per month. The overall annual number of infections was three, with no significant difference between SCIg and IVIg. Side effect incidence rates for IVIg and SCIg were almost identical, though there were significant differences in the incidence rates of specific side effects. Patient quality-oflife surveys showed that most patients felt positive about their infusions, though differences in perceptions of baseline effectiveness and infusion pain by route were noted. CONCLUSIONS: Overall, patients reported good infection control, low side-effect rates, and positive quality-of-life assessments on Ig therapy. The IDEaL Patient Registry provides a real-world population of PID patients with a heterogeneous baseline presentation. Outcomes data on this population provides important feedback on Ig therapy, and may offer insights into patients’ baseline status and their treatment optimization.
Concomitant FMF and TRAPS Mutation In a Periodic Fever Patient Dr. Adrianne C. Netterville, MD1, Dr. Victoria Dimitriades, MD1, Dr. Paul D. Niolet, MD2; 1Louisiana State University Department of Pediatrics, New Orleans, LA, 2Allergy Asthma and Immunology, Ocean Springs, MS. RATIONALE: Familial Mediterranean Fever (FMF) and TNF-Receptor Associated Periodic Syndrome (TRAPS) are two autoinflammatory disorders characterized by unprovoked inflammatory events without high titer autoantibodies. We report a case of recurrent fevers consistent with periodic fever syndrome. On genetic analysis she was found to be heterozygous for two different variants: one each in the MEFV (FMF) and TNFRSF1A (TRAPS) genes. METHODS: DNA PCR and sequencing of periodic fever syndrome panel performed by GeneDx. RESULTS: This is a 2 year old female with recurrent fevers every 3-4 weeks for over one year with bouts lasting 3 days. These episodes varied in nature, and included pharyngitis, mouth ulcers, intermittent diaper rash, leg pain, and abdominal distension. Additionally, not in conjunction with fevers, she experienced erysipelas like rashes. Initial lab work including inflammatory markers and immunity workup were normal. With her clinical history and absence of infection, malignancy, or autoimmune disease, a periodic fever syndrome panel was sent. Genetic analysis revealed that she was heterozygous for two gene variants, I591T mutation in the MEFV (FMF) and R92Q mutation in the TNFRSF1A (TRAPS). Given the above findings it was believed that she was suffering from a mild form of Familial Mediterranean Fever (FMF). She was placed on a trial of colchicine, and has not had any recurrent fevers to date. CONCLUSIONS: This case illustrates that different mutations in the periodic fever syndrome panel can coexist together. Although FMF and TRAPS are treated differently, our patient clinically manifested as FMF and therefore was treated with colchicine.
634
636
MONDAY
Retrospective Analysis Of The Clinical Utility Of Biweekly Dosing With High-Concentration Subcutaneous Immunoglobulin In 10 Patients With Primary Immunodeficiency Dr. Richard L. Wasserman, MD, PhD, FAAAAI1, Dr. Shahnaz Fatteh2, Dr. Javaid M. Khan, DO2, Dr. Elie Haddad, MD3; 1Medical City Children’s Hospital, Dallas, TX, 2Larkin Community Hospital, South Miami, FL, 3CHU Sainte-Justine, Montreal, QC, Canada. RATIONALE: Limited data are available to assess if biweekly (every 2 weeks) administration of subcutaneous immunoglobulin (SCIG) is effective in preventing serious bacterial infections (SBIs) while increasing treatment flexibility. METHODS: A retrospective record review of patients with primary immunodeficiency disease (PIDD) who were administered 20% SCIG at biweekly intervals assessed the occurrence of SBIs, general overall patient health, and serum immunoglobulin (Ig) levels at 3 centers. _18 RESULTS: Ten patients (8 females, 2 males) aged 9–46 years (4 were < years) with common variable immunodeficiency (n56) or specific antibody deficiency (n54) were treated with 20% SCIG every 14 days. Total monthly doses ranged from 231–744 mg/kg using 2–8 infusion sites. The duration of infusions ranged from 50 to 180 min. The most recent serum Ig concentrations ranged from 720–1828 mg/dL. To date, total therapy duration has ranged from <1 to >35 months (median approximately 21.5 months). Only 1 patient was hospitalized for pneumonia during her >28 months of biweekly treatment; 9 patients experienced no acute SBIs and did not require hospitalization. Most patients were subjectively evaluated to be in ‘‘fair,’’ ‘‘good,’’ or ‘‘excellent’’ general health during biweekly SCIG therapy. All patients have continued the biweekly dosing regimen. CONCLUSIONS: Biweekly administration of 20% SCIG maintained effective prevention of SBIs and allowed patients with PIDD to experience good general health. Increasing the options for dosing flexibility and individualization with SCIG could improve patient adherence and quality of life.
635
Association Of Interleukin-23 Receptor Single Nucleotide Polymorphisms With Ulcerative Colitis Dr. Mona Hedayat, MD1, Dr. Nasser Ebrahimi Daryani2, Dr. Farnaz Najmi Varzaneh3, Dr. Nima Rezaei, MD, PhD4; 1Boston Children’s Hospital, Boston, MA, 2Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, 3Molecular Immunology Research Center, Department of Immunology, Tehran University of Medical Sciences, 4Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Tehran, Iran. RATIONALE: Over the past decade, considerable progress has been made in understanding the role of mucosal immunity and host genetics in the pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC). Genome wide association studies have showed a highly significant association between interleukin 23 receptor (IL23R) single nucleotide polymorphisms (SNPs) and CD; however, there are contrary results regarding the disease-modifying effects of IL23R variants in UC. This study was performed in a group of patients with UC to test the possible role of IL23R SNPs in conferring susceptibility (or protection) to the disease. METHODS: The study was performed on 77 Iranian adult patients with UC and 78 healthy controls. Eight IL23R SNPs were genotyped, using Real-Time polymerase chain reaction (RT-PCR). The frequencies of alleles and genotypes at each position were determined and compared between two groups of patients and controls. RESULTS: The frequency of the Tallele at position rs1343151 was significantly higher in the patient group, compared to the controls (p50.018). The TT genotype at the same position was also significantly overrepresented in the patient group (p50.02). There was no significant difference in alleles and genotypes frequencies of other SNPs between patients and controls. CONCLUSIONS: This study identified a new susceptibility locus associated with UC. Our findings provide further insight into the genetics of UC, which might be amenable to future therapeutic intervention.
J ALLERGY CLIN IMMUNOL FEBRUARY 2014
633
The Immunoglobulin Diagnosis, Evaluation, and Key Learnings (IDEaL) Patient Registry: Analysis Of Ig Dosing, Infection Control, and Quality-Of-Life Assessments In Our Primary Immunodeficiency Population Sean Kearns, PhD1, Keith Crawford1, Loretta Kristofek, RN1, Robbyn Kirylo1, Dr. Luqman Seidu, MD2; 1Coram Clinical Trials, Denver, CO, 2 Allergy and Asthma of Atlanta, LLC, Atlanta, GA. RATIONALE: The IDEaL Patient Registry collects longitudinal information on patients receiving immunoglobulin (Ig) replacement therapy from Coram Specialty Infusion Services in an alternate care setting. This poster is focused on Ig dosing, infection control, and quality-of-life assessments in the primary immune deficiency (PID) population. METHODS: Patients of our 138 investigators are eligible for the Registry. With patient consent acquired, patient information from July 2010 onward that had been collected by Coram providers was entered into the IDEaL database. Additionally, patients were asked to complete an SF-36 questionnaire and an LQIQ survey every six months. RESULTS: As of August 2013, 235 PID patients were enrolled. The average dose for SCIg was 135 mg/kg per week, and for IVIg, 409 mg/kg per month. The overall annual number of infections was three, with no significant difference between SCIg and IVIg. Side effect incidence rates for IVIg and SCIg were almost identical, though there were significant differences in the incidence rates of specific side effects. Patient quality-oflife surveys showed that most patients felt positive about their infusions, though differences in perceptions of baseline effectiveness and infusion pain by route were noted. CONCLUSIONS: Overall, patients reported good infection control, low side-effect rates, and positive quality-of-life assessments on Ig therapy. The IDEaL Patient Registry provides a real-world population of PID patients with a heterogeneous baseline presentation. Outcomes data on this population provides important feedback on Ig therapy, and may offer insights into patients’ baseline status and their treatment optimization.
Concomitant FMF and TRAPS Mutation In a Periodic Fever Patient Dr. Adrianne C. Netterville, MD1, Dr. Victoria Dimitriades, MD1, Dr. Paul D. Niolet, MD2; 1Louisiana State University Department of Pediatrics, New Orleans, LA, 2Allergy Asthma and Immunology, Ocean Springs, MS. RATIONALE: Familial Mediterranean Fever (FMF) and TNF-Receptor Associated Periodic Syndrome (TRAPS) are two autoinflammatory disorders characterized by unprovoked inflammatory events without high titer autoantibodies. We report a case of recurrent fevers consistent with periodic fever syndrome. On genetic analysis she was found to be heterozygous for two different variants: one each in the MEFV (FMF) and TNFRSF1A (TRAPS) genes. METHODS: DNA PCR and sequencing of periodic fever syndrome panel performed by GeneDx. RESULTS: This is a 2 year old female with recurrent fevers every 3-4 weeks for over one year with bouts lasting 3 days. These episodes varied in nature, and included pharyngitis, mouth ulcers, intermittent diaper rash, leg pain, and abdominal distension. Additionally, not in conjunction with fevers, she experienced erysipelas like rashes. Initial lab work including inflammatory markers and immunity workup were normal. With her clinical history and absence of infection, malignancy, or autoimmune disease, a periodic fever syndrome panel was sent. Genetic analysis revealed that she was heterozygous for two gene variants, I591T mutation in the MEFV (FMF) and R92Q mutation in the TNFRSF1A (TRAPS). Given the above findings it was believed that she was suffering from a mild form of Familial Mediterranean Fever (FMF). She was placed on a trial of colchicine, and has not had any recurrent fevers to date. CONCLUSIONS: This case illustrates that different mutations in the periodic fever syndrome panel can coexist together. Although FMF and TRAPS are treated differently, our patient clinically manifested as FMF and therefore was treated with colchicine.
634
636
MONDAY
Retrospective Analysis Of The Clinical Utility Of Biweekly Dosing With High-Concentration Subcutaneous Immunoglobulin In 10 Patients With Primary Immunodeficiency Dr. Richard L. Wasserman, MD, PhD, FAAAAI1, Dr. Shahnaz Fatteh2, Dr. Javaid M. Khan, DO2, Dr. Elie Haddad, MD3; 1Medical City Children’s Hospital, Dallas, TX, 2Larkin Community Hospital, South Miami, FL, 3CHU Sainte-Justine, Montreal, QC, Canada. RATIONALE: Limited data are available to assess if biweekly (every 2 weeks) administration of subcutaneous immunoglobulin (SCIG) is effective in preventing serious bacterial infections (SBIs) while increasing treatment flexibility. METHODS: A retrospective record review of patients with primary immunodeficiency disease (PIDD) who were administered 20% SCIG at biweekly intervals assessed the occurrence of SBIs, general overall patient health, and serum immunoglobulin (Ig) levels at 3 centers. _18 RESULTS: Ten patients (8 females, 2 males) aged 9–46 years (4 were < years) with common variable immunodeficiency (n56) or specific antibody deficiency (n54) were treated with 20% SCIG every 14 days. Total monthly doses ranged from 231–744 mg/kg using 2–8 infusion sites. The duration of infusions ranged from 50 to 180 min. The most recent serum Ig concentrations ranged from 720–1828 mg/dL. To date, total therapy duration has ranged from <1 to >35 months (median approximately 21.5 months). Only 1 patient was hospitalized for pneumonia during her >28 months of biweekly treatment; 9 patients experienced no acute SBIs and did not require hospitalization. Most patients were subjectively evaluated to be in ‘‘fair,’’ ‘‘good,’’ or ‘‘excellent’’ general health during biweekly SCIG therapy. All patients have continued the biweekly dosing regimen. CONCLUSIONS: Biweekly administration of 20% SCIG maintained effective prevention of SBIs and allowed patients with PIDD to experience good general health. Increasing the options for dosing flexibility and individualization with SCIG could improve patient adherence and quality of life.
635
Association Of Interleukin-23 Receptor Single Nucleotide Polymorphisms With Ulcerative Colitis Dr. Mona Hedayat, MD1, Dr. Nasser Ebrahimi Daryani2, Dr. Farnaz Najmi Varzaneh3, Dr. Nima Rezaei, MD, PhD4; 1Boston Children’s Hospital, Boston, MA, 2Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, 3Molecular Immunology Research Center, Department of Immunology, Tehran University of Medical Sciences, 4Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Tehran, Iran. RATIONALE: Over the past decade, considerable progress has been made in understanding the role of mucosal immunity and host genetics in the pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC). Genome wide association studies have showed a highly significant association between interleukin 23 receptor (IL23R) single nucleotide polymorphisms (SNPs) and CD; however, there are contrary results regarding the disease-modifying effects of IL23R variants in UC. This study was performed in a group of patients with UC to test the possible role of IL23R SNPs in conferring susceptibility (or protection) to the disease. METHODS: The study was performed on 77 Iranian adult patients with UC and 78 healthy controls. Eight IL23R SNPs were genotyped, using Real-Time polymerase chain reaction (RT-PCR). The frequencies of alleles and genotypes at each position were determined and compared between two groups of patients and controls. RESULTS: The frequency of the Tallele at position rs1343151 was significantly higher in the patient group, compared to the controls (p50.018). The TT genotype at the same position was also significantly overrepresented in the patient group (p50.02). There was no significant difference in alleles and genotypes frequencies of other SNPs between patients and controls. CONCLUSIONS: This study identified a new susceptibility locus associated with UC. Our findings provide further insight into the genetics of UC, which might be amenable to future therapeutic intervention.