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An Unusual Immunoglobulin Profile in an Adult Patient
Abstracts S175
681
T Lymphocyte Profile in Schwachman Diamond Syndrome
R. Sullivan, N. Y. Olson; Pediatrics, University of Kansas, Kansas City, KS. RATIONALE: We report T lymphocyte abnormalities in a patient with cyclic neutropenia and pancreatic dysfunction as part of Schwachman Diamond Syndrome. METHODS: This is a 5.5 month old male who presented to our clinic with symptoms of monthly fevers, diarrhea, emesis, abdominal pain, gas, rash, and thrush. RESULTS: His initial laboratory evaluation included WBC 9.6, neutrophils 16% (ANC 1500), lymphocytes 74%, monocytes 6%, eosinophils 4%, IgA 14mg/dl, amylase 198u/L, lipase normal, liver function normal. Weekly CBCs initially and again at 17 months of age demonstrated 36 day neutropenia cycles. ImmunoCAP RAST to egg -class 3, milk and wheatclass 2 were noted however the patient’s diet was already restricted (breast milk, elemental formula). Laboratory studies IgG, IgM, and IgG subclasses normal, IgA repeat at19 months normal, amylase measurements all elevated. Mitogens (PHA, ConA, PWM) done by 3H-thymidine incorporation were normal. T lymphocyte subsets: ...Age 10 months .............19 months ...% (absolute count) ........% (absolute count) ...CD3 66.4% (3144)...... 57.6% (2448) ...CD4 48.4% (2143) ......42.6% (1787) ...CD8 16.5% (733) .......13% (545) ...CD19 21.4% (1078) ....35.8% (1542) ...CD16/56 9.7% (487) ...2.6% (127) CONCLUSIONS: Pancytopenias in Schwachman Diamond patients may as in this patient be selective and should be further studied. In animal models of pancreatitis pancreatic infiltration with CD8 positive cells has been demonstrated and may provide a partial explanation for the low CD8 count in this case. As leukemia may develop in Schwachman Diamond patients if predictors such as a low CD16/56 can be identified this would be clinically important.
682
An Unusual Immunoglobulin Profile in an Adult Patient
R. Ayuso; Allergy and Clinical Immunology, Mount Sinai Medical Center, NY, NY. A 49-year-old patient was evaluated for recurrent laryngitis, sinusitis and bronchitis throughout his life and two pneumonias in the last two years. He was an athletic man with an unremarkable physical examination. Immunological evaluation showed IgG 1760 mg/dL, IgA 24 mg/dL, IgM 21 mg/dL, IgG1 1400 mg/dL, IgG2 29 mg/dL, IgG3 12 mg/dL, and IgG4 1mg/dL. Specific antibodies to pneumococcal serotypes were non-protective for 12/12 serotypes pre and post immunization. Antibody titers to Haemophilus influenza were non-protective, but protective for tetanus, diphtheria, varicella, mumps and rubella. HIV testing was negative. A CBC was normal. Lymphocyte evaluation showed mildly decreased numbers of B cells and T cells with a normal CD4/CD8 ratio. A random urine protein and immunofixation in urine for light chains, lambda and kappa were negative. However, a serum protein electrophoresis demonstrated a IgG lambda monoclonal paraprotein. A bone marrow biopsy was positive for multiple myeloma with 35% plasma cells. CONCLUSIONS: this patient presents with an unusual immunoglobulin profile with low IgA, IgM, and IgG subclases except normal IgG1, who presented with recurrent infections for evaluation of immunodeficiency. The suspected immunodeficiency was the key to the ultimate diagnosis of multiple myeloma, which was still asymptomatic at that stage. Extreme skewing of IgG subclasses found in the context of recurrent infections and antibody deficiency is an unusual presentation of multiple myeloma but this possibility should be considered in adult patients presenting for immunological evaluation.
683
Ulcerative Colitis in a Pediatric Patient with IgA Deficiency
A. Kounavis1, T. B. Fausnight2; 1Pediatrics, Penn State Children’s Hospital, Hershey, PA, 2Pediatric Asthma and Immunology, Penn State Children’s Hospital, Hershey, PA. RATIONALE: Ulcerative colitis is an inflammatory bowel disease (IBD) and is uncommon in the pediatric age group, with an incidence of 2 cases per 100,000 children. Immunodeficency has been partially implicated in the pathogenesis of IBD, and the association of IgA deficiency with IBD has been reported. Celiac disease is more common in pediatric patients and an association with IgA deficiency is well established. METHODS: A literature review of PubMed for IgA deficiency, IBD, and ulcerative colitis was performed. We describe a 13 year-old female with ulcerative colitis and IgA deficiency who presented for evaluation of chronic diarrhea. RESULTS: IgA deficiency in pediatric patients with inflammatory bowel disease has been reported in the literature. Our patient presented with a several year history of diarrhea thought to be due to food allergy. She also had two cousins with celiac disease. Studies for celiac disease demonstrated an elevated anti-gliaden IgG level and low total IgA level. RAST and skin testing for foods was negative. ESR was elevated (48). She was mildly anemic but her cell counts were otherwise normal. Stool studies for ova and parasites and Giardia antigen were negative. She was subsequently referred to gastroenterology. Upper endoscopy was negative for celiac disease. A colon biopsy was consistent with ulcerative colitis. CONCLUSIONS: IgA deficiency is frequently associated with celiac disease but may also be observed in IBD. Though uncommon, the diagnosis of IBD should be considered when evaluating IgA deficient children with gastrointestinal symptoms and a negative food allergy and infectious disease work-up. Funding: Penn State Children’s Hospital Skeletal Abnormalities Associated with DiGeorge Syndrome: Report of an Unusual Case S. J. Khiani1, J. A. Kleinfeld2, K. J. Khiani3, A. T. Gewurz2; 1Immunology/ Microbiology (RUMC) & Pediatrics (SHCC), Rush University Medical Center-Stroger Hospital of Cook County A/I Program, Chicago, IL, 2Immunology/Microbiology (RUMC) & Pediatrics (SHCC)), Rush University Medical Center-Stroger Hospital of Cook County A/I Program, Chicago, IL, 3Radiology, Geisinger Medical Center, Danville, PA. INTRODUCTION: Skeletal abnormalities have been demonstrated in several primary immunodeficiency disorders, but are not considered characteristic of DiGeorge syndrome (DGS). We describe a case of DGS presenting with extensive bone defects and discuss the possible significance of this association. CASE REPORT AND LITERATURE REVIEW: A male infant was delivered at 36 weeks gestation with truncus arteriosus, hypocalcemia, lymphopenia and thymus hypoplasia, diagnosed as DGS, to a 24yo G2P001 hypothyroid, diabetic, smoking mother. Genetic analysis showed 46XY karyotype and no deletion (by FISH) of the 22q11 or 10p13 loci. Chest radiograms showed butterfly defects of the T6, T8, and T12 vertebrae; a small, hypodense T10 vertebral body; an asymmetric L4 vertebra; mild mid/inferior thoracic levoscoliosis; a hypoplastic left 7th rib, and a wide gap between the left 7th and 8th ribs. A Medline search conducted using PubMed and other search engines identified multiple reports during the past 10 years of axial skeletal and other bone abnormalities associated with DGS and deletion of 22q11. Mutations of the T-box 1 gene TBX1, located near or within the 22q11 locus, may be responsible for the bone defects associated with DGS, as well as the classic DGS phenotype itself, although other genes may also play a role. CONCLUSIONS: As illustrated by this case, vertebral and other bone abnormalities may be a more common and fundamental feature of DGS than is presently appreciated. This patient may be unique, in that he has DGS with extensive skeletal anomalies, but no detectable deletion of the 22q11 or 10p13 loci. Funding: Rush University Medical Center
684
SUNDAY
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2
681
T Lymphocyte Profile in Schwachman Diamond Syndrome
R. Sullivan, N. Y. Olson; Pediatrics, University of Kansas, Kansas City, KS. RATIONALE: We report T lymphocyte abnormalities in a patient with cyclic neutropenia and pancreatic dysfunction as part of Schwachman Diamond Syndrome. METHODS: This is a 5.5 month old male who presented to our clinic with symptoms of monthly fevers, diarrhea, emesis, abdominal pain, gas, rash, and thrush. RESULTS: His initial laboratory evaluation included WBC 9.6, neutrophils 16% (ANC 1500), lymphocytes 74%, monocytes 6%, eosinophils 4%, IgA 14mg/dl, amylase 198u/L, lipase normal, liver function normal. Weekly CBCs initially and again at 17 months of age demonstrated 36 day neutropenia cycles. ImmunoCAP RAST to egg -class 3, milk and wheatclass 2 were noted however the patient’s diet was already restricted (breast milk, elemental formula). Laboratory studies IgG, IgM, and IgG subclasses normal, IgA repeat at19 months normal, amylase measurements all elevated. Mitogens (PHA, ConA, PWM) done by 3H-thymidine incorporation were normal. T lymphocyte subsets: ...Age 10 months .............19 months ...% (absolute count) ........% (absolute count) ...CD3 66.4% (3144)...... 57.6% (2448) ...CD4 48.4% (2143) ......42.6% (1787) ...CD8 16.5% (733) .......13% (545) ...CD19 21.4% (1078) ....35.8% (1542) ...CD16/56 9.7% (487) ...2.6% (127) CONCLUSIONS: Pancytopenias in Schwachman Diamond patients may as in this patient be selective and should be further studied. In animal models of pancreatitis pancreatic infiltration with CD8 positive cells has been demonstrated and may provide a partial explanation for the low CD8 count in this case. As leukemia may develop in Schwachman Diamond patients if predictors such as a low CD16/56 can be identified this would be clinically important.
682
An Unusual Immunoglobulin Profile in an Adult Patient
R. Ayuso; Allergy and Clinical Immunology, Mount Sinai Medical Center, NY, NY. A 49-year-old patient was evaluated for recurrent laryngitis, sinusitis and bronchitis throughout his life and two pneumonias in the last two years. He was an athletic man with an unremarkable physical examination. Immunological evaluation showed IgG 1760 mg/dL, IgA 24 mg/dL, IgM 21 mg/dL, IgG1 1400 mg/dL, IgG2 29 mg/dL, IgG3 12 mg/dL, and IgG4 1mg/dL. Specific antibodies to pneumococcal serotypes were non-protective for 12/12 serotypes pre and post immunization. Antibody titers to Haemophilus influenza were non-protective, but protective for tetanus, diphtheria, varicella, mumps and rubella. HIV testing was negative. A CBC was normal. Lymphocyte evaluation showed mildly decreased numbers of B cells and T cells with a normal CD4/CD8 ratio. A random urine protein and immunofixation in urine for light chains, lambda and kappa were negative. However, a serum protein electrophoresis demonstrated a IgG lambda monoclonal paraprotein. A bone marrow biopsy was positive for multiple myeloma with 35% plasma cells. CONCLUSIONS: this patient presents with an unusual immunoglobulin profile with low IgA, IgM, and IgG subclases except normal IgG1, who presented with recurrent infections for evaluation of immunodeficiency. The suspected immunodeficiency was the key to the ultimate diagnosis of multiple myeloma, which was still asymptomatic at that stage. Extreme skewing of IgG subclasses found in the context of recurrent infections and antibody deficiency is an unusual presentation of multiple myeloma but this possibility should be considered in adult patients presenting for immunological evaluation.
683
Ulcerative Colitis in a Pediatric Patient with IgA Deficiency
A. Kounavis1, T. B. Fausnight2; 1Pediatrics, Penn State Children’s Hospital, Hershey, PA, 2Pediatric Asthma and Immunology, Penn State Children’s Hospital, Hershey, PA. RATIONALE: Ulcerative colitis is an inflammatory bowel disease (IBD) and is uncommon in the pediatric age group, with an incidence of 2 cases per 100,000 children. Immunodeficency has been partially implicated in the pathogenesis of IBD, and the association of IgA deficiency with IBD has been reported. Celiac disease is more common in pediatric patients and an association with IgA deficiency is well established. METHODS: A literature review of PubMed for IgA deficiency, IBD, and ulcerative colitis was performed. We describe a 13 year-old female with ulcerative colitis and IgA deficiency who presented for evaluation of chronic diarrhea. RESULTS: IgA deficiency in pediatric patients with inflammatory bowel disease has been reported in the literature. Our patient presented with a several year history of diarrhea thought to be due to food allergy. She also had two cousins with celiac disease. Studies for celiac disease demonstrated an elevated anti-gliaden IgG level and low total IgA level. RAST and skin testing for foods was negative. ESR was elevated (48). She was mildly anemic but her cell counts were otherwise normal. Stool studies for ova and parasites and Giardia antigen were negative. She was subsequently referred to gastroenterology. Upper endoscopy was negative for celiac disease. A colon biopsy was consistent with ulcerative colitis. CONCLUSIONS: IgA deficiency is frequently associated with celiac disease but may also be observed in IBD. Though uncommon, the diagnosis of IBD should be considered when evaluating IgA deficient children with gastrointestinal symptoms and a negative food allergy and infectious disease work-up. Funding: Penn State Children’s Hospital Skeletal Abnormalities Associated with DiGeorge Syndrome: Report of an Unusual Case S. J. Khiani1, J. A. Kleinfeld2, K. J. Khiani3, A. T. Gewurz2; 1Immunology/ Microbiology (RUMC) & Pediatrics (SHCC), Rush University Medical Center-Stroger Hospital of Cook County A/I Program, Chicago, IL, 2Immunology/Microbiology (RUMC) & Pediatrics (SHCC)), Rush University Medical Center-Stroger Hospital of Cook County A/I Program, Chicago, IL, 3Radiology, Geisinger Medical Center, Danville, PA. INTRODUCTION: Skeletal abnormalities have been demonstrated in several primary immunodeficiency disorders, but are not considered characteristic of DiGeorge syndrome (DGS). We describe a case of DGS presenting with extensive bone defects and discuss the possible significance of this association. CASE REPORT AND LITERATURE REVIEW: A male infant was delivered at 36 weeks gestation with truncus arteriosus, hypocalcemia, lymphopenia and thymus hypoplasia, diagnosed as DGS, to a 24yo G2P001 hypothyroid, diabetic, smoking mother. Genetic analysis showed 46XY karyotype and no deletion (by FISH) of the 22q11 or 10p13 loci. Chest radiograms showed butterfly defects of the T6, T8, and T12 vertebrae; a small, hypodense T10 vertebral body; an asymmetric L4 vertebra; mild mid/inferior thoracic levoscoliosis; a hypoplastic left 7th rib, and a wide gap between the left 7th and 8th ribs. A Medline search conducted using PubMed and other search engines identified multiple reports during the past 10 years of axial skeletal and other bone abnormalities associated with DGS and deletion of 22q11. Mutations of the T-box 1 gene TBX1, located near or within the 22q11 locus, may be responsible for the bone defects associated with DGS, as well as the classic DGS phenotype itself, although other genes may also play a role. CONCLUSIONS: As illustrated by this case, vertebral and other bone abnormalities may be a more common and fundamental feature of DGS than is presently appreciated. This patient may be unique, in that he has DGS with extensive skeletal anomalies, but no detectable deletion of the 22q11 or 10p13 loci. Funding: Rush University Medical Center
684
SUNDAY
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2