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INTERFERON GAMMA RECEPTOR 1 DEFICIENCY (IFNGR1) WITH NEGATIVE QUANTIFERON GOLD AND ELEVATED C-REACTIVE PROTEIN
Abstracts: Medically Challenging Cases / Ann Allergy Asthma Immunol 121 (2018) S63−S134
including autoimmune pneumonitis, have shown improvement in other similar cases with mycophenolate treatment. This case demonstrates APS Type 1 improvement with mycophenolate therapy.
M256
are associated with aspiration pneumonia. Patients with DS can develop immune deficiency of varying degrees. Further immune workup including T lymphocyte functional testing and convalescent titers post-pneumococcal polysaccharide vaccine is pending. Treatment for immune deficiency may be indicated based on results. Lung abscess should be considered in the differential diagnosis for patients with DS presenting with acute respiratory illness and protracted fever.
IMMUNODEFICIENCY IN PATIENTS WITH MYASTHENIA GRAVIS AND A THYMOMA R. Tamayev*1, S. Nassau2, A. Rubinstein1, 1. Bronx, NY; 2. Mineola, NY Introduction: Thymomas are a well-described concurrence in patients with Myasthenia Gravis. We describe two adult patients with Myasthenia Gravis and a thymoma who have undergone a total thymectomy and were found to have immune dysregulation. Case Description: Two patients with years of recurrent infections were subsequently diagnosed with Myasthenia Gravis and a thymoma. Years after their thymectomies, they were found to have divergent immune aberrations. Patient 1 had decreased CD19+B cells (2%), and increased CD8+T cells (52%), associated with hypergammaglobulinemia, MGUS, and poor antibody responses to polysaccharide antigens. Patient 2 was hypogammaglobulinemic (IgG, IgM) with markedly increased CD19+ B cells (32%), low switched memory B cells-8% (normal 19-53%), decreased CD8+ T cells (2%) with normal na€ıve, memory CD4+, CD8+, and TEMRA T cells. She also had poor antibody responses to polysaccharide antigens. Genetics for TACI and CTLA-4 were negative. Both patients were studied years post-thymectomy with no known immune studies pre-thymectomy. Discussion: We describe two patients with a history of recurrent, poorly controlled infections and Myasthenia Gravis. Both patients presented with divergent immune abnormalities. These patients are different in their presentation from Good’s syndrome, a separate immune deficiency with a thymoma often associated with Myasthenia Gravis. In general, thymectomy even in infants is not involved in marked immune aberrations except for precocious mild immune senescence with low memory CD3+CD8+CD57+ T cells. It is therefore unlikely that the immune aberrations in our patients are related to the thymectomy, but rather represent two new divergent immune aberrations leading to Myasthenia Gravis.
M257 A SIX-YEAR-OLD MALE WITH DOWN SYNDROME AND ACUTE LUNG ABSCESS N. Sirohi*1, S. Blumer2, M. DeFelice2, 1. Glen Mills, PA; 2. Wilmington, DE Introduction: Children with Down syndrome (DS) are at risk for recurrent and severe respiratory tract infections, however lung abscesses are not commonly reported. Case Description: The patient is a six-year-old male with DS, asthma, obstructive sleep apnea, atrioventricular canal defect status post repair, admitted with two days of fever and cough. Examination revealed hypoxia and tachypnea. Chest x-ray showed right upper lobe (RUL) opacity concerning for pneumonia, thought to be due to rhinovirus/enterovirus. Fever persisted despite corticosteroids and respiratory medications. Chest CT scan revealed large RUL abscess with mediastinal shift and compression of the trachea and right atrium (Figure 1). Antibiotics were initiated with gradual improvement. There was no prior history of bacterial pneumonia or serious bacterial infection. Flow cytometry revealed T (CD3+ 779 cells/mL) and B cell (CD19+ 130 cells/mL) lymphopenia. Quantitative immunoglobulins, neutrophil oxidative burst, and CD18 expression were normal. Tetanus titer was protective. Pneumococcal titers showed 3/23 (0/11 non-pneumococcal conjugate vaccine) serotypes protective. Discussion: Lung abscess is not a common infection in children with DS. Additionally, the acute presentation of RUL abscess in this patient is unusual; lung abscesses often present with indolent symptoms and
S103
CT Chest with Contrast
Axial image from a contrast-enhanced chest CT scan reveals an intraparenchymal pulmonary abscess with internal air-fluid levels and peripheral wall enhancement causing right to left mass effect and mediastinal shift with mild compression of the carina.
M258 INTERFERON GAMMA RECEPTOR 1 DEFICIENCY (IFNGR1) WITH NEGATIVE QUANTIFERON GOLD AND ELEVATED C-REACTIVE PROTEIN I. DuBuske*, C. McKnight, Cincinnati, OH Introduction: Defects in IFNGR1 leads to Mendelian Susceptibility to Mycobacterial Disease. The extent of reduction of IFNGR1 determines the phenotype of disease expression. Mutations occurring in Autosomal Dominant IFNGR1 deficiency lead to non-functional receptors on cell surfaces which fail to transduce IFNG signals. These patients are older than those with Autosomal Recessive complete IFGR1 deficiency, with later onset, less severe mycobacteria infections but high prevalence (79%) of non-tuberculous mycobacterial (NTM) osteomyelitis. Case Description: A 30-year old male from United Arab Emirates presented with recurrent atypical mycobacteria infections for over 20 years, having multiple courses of anti-TB therapy. Therapy with IFNG from 2009 to 2011 was discontinued due to adverse effects. Gene sequencing identified a pathogenic variant in the IFNGR1 gene in a heterozygous state at c.819ç822del p. (Asn274Hisfs*2) creating a shift in the reading frame starting at codon 274, with the new reading frame ending in a stop codon 2 position downstream causing autosomal dominant (AD) immunodeficiency type 27B mycobacteriosis. His QuantiFERON Gold test was negative despite the history of TB. C-reactive protein (CRP) was elevated at 74.6. His CD4, CD8 and CD3 absolute counts were normal. MRI scan of the thoracic spine showed multifocal areas of thoracic vertebral marrow infiltration. Discussion: AD IFNGR1 deficiency leads often to NTM osteomyelitis as suspected in this case. Neither CRP elevation nor accuracy of the QuantiFERON Gold test have been reported in AD IFNGR1 deficiency patients. This case suggests QuantiFERON Gold test performance may be impaired in these patients.
including autoimmune pneumonitis, have shown improvement in other similar cases with mycophenolate treatment. This case demonstrates APS Type 1 improvement with mycophenolate therapy.
M256
are associated with aspiration pneumonia. Patients with DS can develop immune deficiency of varying degrees. Further immune workup including T lymphocyte functional testing and convalescent titers post-pneumococcal polysaccharide vaccine is pending. Treatment for immune deficiency may be indicated based on results. Lung abscess should be considered in the differential diagnosis for patients with DS presenting with acute respiratory illness and protracted fever.
IMMUNODEFICIENCY IN PATIENTS WITH MYASTHENIA GRAVIS AND A THYMOMA R. Tamayev*1, S. Nassau2, A. Rubinstein1, 1. Bronx, NY; 2. Mineola, NY Introduction: Thymomas are a well-described concurrence in patients with Myasthenia Gravis. We describe two adult patients with Myasthenia Gravis and a thymoma who have undergone a total thymectomy and were found to have immune dysregulation. Case Description: Two patients with years of recurrent infections were subsequently diagnosed with Myasthenia Gravis and a thymoma. Years after their thymectomies, they were found to have divergent immune aberrations. Patient 1 had decreased CD19+B cells (2%), and increased CD8+T cells (52%), associated with hypergammaglobulinemia, MGUS, and poor antibody responses to polysaccharide antigens. Patient 2 was hypogammaglobulinemic (IgG, IgM) with markedly increased CD19+ B cells (32%), low switched memory B cells-8% (normal 19-53%), decreased CD8+ T cells (2%) with normal na€ıve, memory CD4+, CD8+, and TEMRA T cells. She also had poor antibody responses to polysaccharide antigens. Genetics for TACI and CTLA-4 were negative. Both patients were studied years post-thymectomy with no known immune studies pre-thymectomy. Discussion: We describe two patients with a history of recurrent, poorly controlled infections and Myasthenia Gravis. Both patients presented with divergent immune abnormalities. These patients are different in their presentation from Good’s syndrome, a separate immune deficiency with a thymoma often associated with Myasthenia Gravis. In general, thymectomy even in infants is not involved in marked immune aberrations except for precocious mild immune senescence with low memory CD3+CD8+CD57+ T cells. It is therefore unlikely that the immune aberrations in our patients are related to the thymectomy, but rather represent two new divergent immune aberrations leading to Myasthenia Gravis.
M257 A SIX-YEAR-OLD MALE WITH DOWN SYNDROME AND ACUTE LUNG ABSCESS N. Sirohi*1, S. Blumer2, M. DeFelice2, 1. Glen Mills, PA; 2. Wilmington, DE Introduction: Children with Down syndrome (DS) are at risk for recurrent and severe respiratory tract infections, however lung abscesses are not commonly reported. Case Description: The patient is a six-year-old male with DS, asthma, obstructive sleep apnea, atrioventricular canal defect status post repair, admitted with two days of fever and cough. Examination revealed hypoxia and tachypnea. Chest x-ray showed right upper lobe (RUL) opacity concerning for pneumonia, thought to be due to rhinovirus/enterovirus. Fever persisted despite corticosteroids and respiratory medications. Chest CT scan revealed large RUL abscess with mediastinal shift and compression of the trachea and right atrium (Figure 1). Antibiotics were initiated with gradual improvement. There was no prior history of bacterial pneumonia or serious bacterial infection. Flow cytometry revealed T (CD3+ 779 cells/mL) and B cell (CD19+ 130 cells/mL) lymphopenia. Quantitative immunoglobulins, neutrophil oxidative burst, and CD18 expression were normal. Tetanus titer was protective. Pneumococcal titers showed 3/23 (0/11 non-pneumococcal conjugate vaccine) serotypes protective. Discussion: Lung abscess is not a common infection in children with DS. Additionally, the acute presentation of RUL abscess in this patient is unusual; lung abscesses often present with indolent symptoms and
S103
CT Chest with Contrast
Axial image from a contrast-enhanced chest CT scan reveals an intraparenchymal pulmonary abscess with internal air-fluid levels and peripheral wall enhancement causing right to left mass effect and mediastinal shift with mild compression of the carina.
M258 INTERFERON GAMMA RECEPTOR 1 DEFICIENCY (IFNGR1) WITH NEGATIVE QUANTIFERON GOLD AND ELEVATED C-REACTIVE PROTEIN I. DuBuske*, C. McKnight, Cincinnati, OH Introduction: Defects in IFNGR1 leads to Mendelian Susceptibility to Mycobacterial Disease. The extent of reduction of IFNGR1 determines the phenotype of disease expression. Mutations occurring in Autosomal Dominant IFNGR1 deficiency lead to non-functional receptors on cell surfaces which fail to transduce IFNG signals. These patients are older than those with Autosomal Recessive complete IFGR1 deficiency, with later onset, less severe mycobacteria infections but high prevalence (79%) of non-tuberculous mycobacterial (NTM) osteomyelitis. Case Description: A 30-year old male from United Arab Emirates presented with recurrent atypical mycobacteria infections for over 20 years, having multiple courses of anti-TB therapy. Therapy with IFNG from 2009 to 2011 was discontinued due to adverse effects. Gene sequencing identified a pathogenic variant in the IFNGR1 gene in a heterozygous state at c.819ç822del p. (Asn274Hisfs*2) creating a shift in the reading frame starting at codon 274, with the new reading frame ending in a stop codon 2 position downstream causing autosomal dominant (AD) immunodeficiency type 27B mycobacteriosis. His QuantiFERON Gold test was negative despite the history of TB. C-reactive protein (CRP) was elevated at 74.6. His CD4, CD8 and CD3 absolute counts were normal. MRI scan of the thoracic spine showed multifocal areas of thoracic vertebral marrow infiltration. Discussion: AD IFNGR1 deficiency leads often to NTM osteomyelitis as suspected in this case. Neither CRP elevation nor accuracy of the QuantiFERON Gold test have been reported in AD IFNGR1 deficiency patients. This case suggests QuantiFERON Gold test performance may be impaired in these patients.