- Email: [email protected]
O012 A single center experience of SCID newborn screening in illinois
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Abstracts: Oral Concurrent Sessions / Ann Allergy Asthma Immunol 117 (2016) S1eS21
O009 SYSTEMIC MASTOCYTOSIS PRESENTING AS CARDIAC TAMPONADE A. Wong*1, J. Toh2, E. Jerschow1, 1. Bronx, NY; 2. New York, NY. Introduction: Systemic mastocytosis (SM) is a rare disorder characterized by the growth and accumulation of pathologic mast cells in one or more organ systems. We describe a patient with undiagnosed SM who presented with pericardial effusion/cardiac tamponade. Methods: Chart review. Results: A 59-year-old man with a twenty-year history of diffuse lymphadenopathy and hyperpigmented macular rash presented with pleuritic chest pain. Medical history included flushing after drinking alcohol and anaphylaxis after NSAID use. Echocardiogram revealed pericardial effusion/cardiac tamponade. An emergent pericardial window drained 1 liter of fluid. The procedure was complicated by intraoperative hypotension from an anaphylactoid reaction necessitating epinephrine. Initial pericardial fluid analysis and biopsy revealed fibroadipose tissue with chronic inflammation and fibrinous exudate. Additional staining of the fluid showed mast cells with aberrant CD25 expression. An elevated tryptase (115 ng/ml) prompted a bone marrow biopsy, revealing dense aggregates of atypical mast cells with aberrant CD25 expression. Skin biopsy showed telangiectasia macularis eruptiva perstans, a form of cutaneous mastocytosis. A previous gastric biopsy was reevaluated, revealing two clusters (>15 mast cells; c-kit positive) of atypical mast cells with aberrant CD25 expression. These findings and a positive peripheral c-kit mutation (D816V) confirmed the diagnosis of SM. His decreased albumin and hepatomegaly classified his SM as the aggressive variant. Conclusion: This is a rare description of an undiagnosed systemic mastocytosis patient presenting with pericardial effusion/cardiac tamponade, likely due to pericarditis from mast cell mediators causing inflammation and subsequent effusion. This potentially life-threatening condition would be an important clinical presentation of SM.
O010 POST-NATAL MECHANISMS OF HUMAN HEMATOPOIETIC STEM CELL SELF-RENEWAL V. Bundy*, S. Sandoval, C. Seet, C. Parekh, C. Chin, C. He, Y. Zhu, L. Kohn, D. Rao, G. Crooks, Los Angeles, CA. Introduction: Hematopoietic stem cell (HSC) transplantation is the only potentially curative, non-experimental therapy available to treat severe primary immunodeficiency disease. Precise regulatory mechanisms to support and maintain HSCs remain to be elucidated. Micro RNAs (miRNAs) have been shown in many systems to regulate stem cell function. This study focuses on miRNA-specific mechanisms that support and maintain HSCs. Methods: Our laboratory has identified a genomic cluster of miRNAs (miR-99a/let-7c/miR-125b) that is highly coexpressed in hematopoietic stem cells, almost absent in progenitors and mature cells, with an expression pattern specific to postnatal hematopoiesis in the adult bone marrow. To determine the impact of increased miRNA expression in human HSCs, we generated lentiviral vectors to overexpress let-7c, miR-125b, or the entire cluster. Results: Lentiviral expression of let-7c alone decreased the number and frequency of CD34+ cells, reduced long-term culture initiation cells (LTC-ICs) and increased myeloid cell output. In contrast, expression of miR-125b alone expanded CD34+ cells and LTC-ICs. Expression of the entire miRNA cluster revealed a phenotype intermediate between let-7c and mir-125b overexpression. We have now also developed lentiviral “sponge” vectors to inhibit each miRNA individually, and hypothesize that inhibition of let-7c will enhance HSC proliferation due to un-opposed miR-125b. Conclusion: Our data suggests that let-7c may inhibit miR-125binduced proliferation during adult hematopoiesis. Our future goal is to use bioinformatics packages that combine miRNA and gene
expression analyses to identify molecular targets of let-7c and miR125b. We will use RNA-Seq to identify early transcriptional changes that occur after both over-expression and knockdown.
O011 IMMUNOGLOBULIN MANAGEMENT APPROACHES IN AMERICAN PATIENTS WITH COMMON VARIABLE IMMUNE DEFICIENCY AND AUTOIMMUNITY K. Kennedy*1, C. Cunningham-Rundles2, M. Morsheimer3, 1. Philadelphia, PA; 2. New York, NY; 3. Wilmington, DE. Introduction: Common variable immune deficiency (CVID) is a primary immune deficiency characterized by B cell dysfunction and paucity of protective specific antibodies. Autoimmunity, and commonly hematologic cytopenias, is also a manifestation. Immunoglobulin replacement therapy is the cornerstone of management; treatment route and dose can be used to modulate the frequency and severity of cytopenias. Typically IV immunoglobulin administration (IVIG) at high doses is required for immunomodulatory benefits, however international experience suggests subcutaneous administration at lower doses can also be successful. We aim to summarize the American experience regarding immunoglobulin route and dosing among CVID subjects with autoimmunity. Methods: A USIDNET enrollment characteristic query of 1494 CVID patients revealed 105 cases with autoimmunity. Variables assessed included sex, autoimmune disorder, transfusion history, adjunctive immunomodulatory medications, and immunoglobulin dose and administration route. STATA performed descriptive statistics. Results: The majority were female (61%) and treated with IVIG (72%). One third had cytopenias, most commonly immune thrombocytopenic purpura (14.2%). Nearly 80% with cytopenias received IVIG (300 to 1300 mg/kg/dose); 67% of these patients required immunomodulatory medications and 18% required transfusions. Approximately 20% with cytopenias were treated with subcutaneous immunoglobulin (SCIG) (100-150mg/kg/dose); 86% of these patients required immunomodulatory medications and 42% required transfusions. Conclusion: Most American CVID patients with cytopenias were managed with IVIG and had lower rates of immunomodulatory medications and transfusions than those on SCIG. There was a wide range of autoimmunity noted in the cohort with the same preference for IVIG noted for non-hematologic complications. Institutional-level data is required to identify characteristics predictive of success on SCIG.
O012 A SINGLE CENTER EXPERIENCE OF SCID NEWBORN SCREENING IN ILLINOIS J. Bergerson*, A. Skoskiewicz, R. Fuleihan, Chicago, IL. Background: Severe combined immunodeficiency (SCID) is primary immunodeficiency that result from the absence or diminished function of T cells. SCID is phenotypically classified by the presence or absence of B and NK cells and each subtype can be caused by defects in a number of different genes. Early diagnosis and prompt treatment of SCID leads to decreased patient mortality from disease complications. In May 2014, Illinois instituted newborn screening (NBS) of all infants for T-cell lymphopenia via Tcell receptor excision circle (TREC) assay. Methods: TREC level was performed as part of the Illinois state NBS program. Infants who had abnormal TREC levels (<300 in year one, and <250 in year two) were referred for further evaluation. Results: We identified patients with SCID, 22q11 deletion syndromes, Trisomy 21, and idiopathic T cell lymphopenia (iTCL) from all infants referred with low TREC levels. Since initiation of statewide newborn screening for SCID we evaluated six infants with absent TREC levels (TREC ¼ 0). Four of these six patients had typical SCID. The two remaining patients had iTCL. One of the patients
Abstracts: Oral Concurrent Sessions / Ann Allergy Asthma Immunol 117 (2016) S1eS21
diagnosed with iTCL has increasing T-cells and the other remains severely lymphopenic. Conclusions: Our data over two years of NBS in Illinois demonstrates that not all patients presenting with absent TREC levels have SCID. However, all of the patients with a diagnosis of SCID had TREC levels of zero. Therefore in our experience newborn screening can correctly identify those individuals with SCID or severe T cell lymphopenia, but additional testing is needed to confirm the diagnosis.
O013 NOVEL RAG-1 MUTATION IDENTIFIED IN A PATIENT WITH HYPOMORPHIC SEVERE COMBINED IMMUNODEFICIENCY (SCID) D. Arnold*, J. Heimall, Philadelphia, PA. Background: TREC newborn screening facilitates early diagnosis of both typical and hypomorphic SCID. Hypomorphic SCID patients often have abnormalities in RAG1/RAG2 enzymes. RAG1/RAG2 mediate the process of VDJ rearrangement in T and B cell progenitors, with defects leading to a T-B-NK+ SCID that can have a highly variable clinical presentation, including classic SCID, Omenn Syndrome and late-onset autoimmunity. Case Presentation: A newborn Caucasian female presented for evaluation due to low but not absent TRECs on state-based newborn screening. Immunology studies demonstrated: CD3 949, CD4 575, CD4/CD45RA 312, CD4/CD45RO 185, CD8 359, CD19 89, CD16/CD56 811; PHA proliferation 72004 CPM. This raised concern for hypomorphic SCID. Genetic testing demonstrated W204X and W522C mutations in the RAG1 gene. The W522C missense mutation has been reported previously in a patient with Omenn Syndrome. However, the W204X mutation has not previously been reported. It is predicted to cause loss of normal protein function through protein truncation. Thus, W204X was considered to be a disease-causing mutation. At 4 months of age, the patient received an unrelated umbilical cord blood transplant (UCB HSCT) following myeloablative conditioning. By 6 months post-transplant, immune studies demonstrated: CD3 1361, CD4 792, CD4/CD45RA 490, CD4/ CD45RO 354, CD8 509, CD19 1699, CD19/CD27/IgD- 23, CD16/CD56 907; PHA proliferation 69215 CPM. IgG was normal for age off IVIG. Engraftment is 100% across T, B and myeloid lineages. At 2.5 years of age, she is alive and well. Discussion: A novel RAG1 W204X mutation was demonstrated in this patient with hypomorphic SCID, who was successfully treated with UCB HSCT.
O014 SPLENOMEGALY AND IGA DEFICIENCY PREDICTS GRANULOMATOUS LYMPHOCYTIC INTERSTITIAL LUNG DISEASE (GLILD) IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) S. Hartono*1, M. Motosue2, S. Khan1, V. Rodriguez1, R. Divekar1, A. Joshi1, 1. Rochester, MN; 2. Honolulu, HI. Introduction: A subset of CVID patients develops granulomatous lymphocytic interstitial lung disease (GLILD), which is associated with early mortality. We sought to determine a set of clinical and laboratory parameters that correlate with GLILD development and progression. Methods: The study is a retrospective nested case (CVID subjects with GLILD)-control (CVID subjects without GLILD) chart review. Network and univariate analysis was used to identify clinical and laboratory parameters at the time of diagnosis that are associated with GLILD. Predictive accuracy of the identified variables was determined by logistic regression. Results: 26 cases with radiologic evidence of GLILD were included in this study. 18/26 (69%) of the cases had co-existent splenomegaly with lower IgA levels (p¼0.04) compared to the controls. Subjects with low IgA (<13 mg/dL) also had expansion of CD21low B cells
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(% CD21low >5) (p¼0.007). Univariate analysis revealed that splenomegaly (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.9 e 74.5), history of autoimmune cytopenia (OR 4.8, 95% CI 1.1 e 20.2), low IgA (OR 3.6, 95% CI 1.2 e 11.9), and expansion of CD21low (OR 5.8, 95% CI 1.6 e 24.7) were independently associated with GLILD. Logistic regression analysis showed that splenomegaly, history of cytopenia (ITP or AIHA), low IgA, and expansion of CD21low B cells are highly sensitive in predicting presence of GLILD (area under the receiver-operating curve of 0.86). Conclusion: Presence of splenomegaly, history of autoimmune cytopenia, low serum IgA, and expansion of CD21low B cells may be useful to identify a group of patients at high risk for development of GLILD.
Figure. Categorical data from abstracted dataset was converted to a bipartite network graph to reveal overview of associations. Incomplete variables were excluded to avoid bias. Gray nodes: GLILD, white nodes: no GLILD. Black squares: clinical variable.
O015 TOLERABILITY OF A NEW HUMAN IMMUNE GLOBULIN SUBCUTANEOUS, 20% PREPARATION IN PRIMARY IMMUNODEFICIENCY DISEASES S. Gupta*1, M. Stein2, I. Melamed3, I. Hussain4, K. Paris5, W. Engl6, B. McCoy7, C. Rabbat8, L. Yel7, 1. Irvine, CA; 2. North Palm Beach, FL; 3. Centennial, CO; 4. Tulsa, OK; 5. New Orleans, LA; 6. Vienna, Austria; 7. Cambridge, MA; 8. Bannockburn, IL. Introduction: Human immune globulin subcutaneous, 20% (SCIG 20%) is a ready-to-use, liquid preparation of highly purified human immunoglobulin G. Local adverse events (AEs) were investigated for potential association with increasing SCIG 20% infusion volumes and rates from a phase 2/3 study in patients with primary immunodeficiency diseases in North America. Methods: Patients received weekly SCIG 20% for up to w1.3 years. Up to 60 mL/site was administered. For patients weighing <40 kg, recommended infusion volumes were <¼20 mL/site (first two infusions) and then <¼60 mL/site (subsequent infusions), as tolerated. Recommended infusion rate for the first two infusions was 10-20 mL/hr/site; subsequent infusions could be increased <¼60 mL/hr/site, as tolerated. Results: Seventy-four patients aged 3-83 years received 4327 SCIG 20% infusions; 98.2% were not associated with a local adverse reaction. There was no association between increasing volume/site (30-39, 40-49, 50-59, and >¼60 mL/site) and causally-related local AE (0.4%, 1.4%, 1.1%, and 0.3%, respectively) rates. In all, 72% of patients reached 60 mL/hr/site, for a median total infusion time of 0.95 hr (53% and 85% of infusions were delivered in <1, and <1.5 hr, respectively). More than half (57%) of infusions were delivered at >¼60 mL/hr/site, with no association between the increasing infusion rates (30-39, 40-49, 50-59, and >¼60 mL/hr/site) and casually-related local AE (0.8%, 0.9%, 4.5%, and 0.4%, respectively)
Abstracts: Oral Concurrent Sessions / Ann Allergy Asthma Immunol 117 (2016) S1eS21
O009 SYSTEMIC MASTOCYTOSIS PRESENTING AS CARDIAC TAMPONADE A. Wong*1, J. Toh2, E. Jerschow1, 1. Bronx, NY; 2. New York, NY. Introduction: Systemic mastocytosis (SM) is a rare disorder characterized by the growth and accumulation of pathologic mast cells in one or more organ systems. We describe a patient with undiagnosed SM who presented with pericardial effusion/cardiac tamponade. Methods: Chart review. Results: A 59-year-old man with a twenty-year history of diffuse lymphadenopathy and hyperpigmented macular rash presented with pleuritic chest pain. Medical history included flushing after drinking alcohol and anaphylaxis after NSAID use. Echocardiogram revealed pericardial effusion/cardiac tamponade. An emergent pericardial window drained 1 liter of fluid. The procedure was complicated by intraoperative hypotension from an anaphylactoid reaction necessitating epinephrine. Initial pericardial fluid analysis and biopsy revealed fibroadipose tissue with chronic inflammation and fibrinous exudate. Additional staining of the fluid showed mast cells with aberrant CD25 expression. An elevated tryptase (115 ng/ml) prompted a bone marrow biopsy, revealing dense aggregates of atypical mast cells with aberrant CD25 expression. Skin biopsy showed telangiectasia macularis eruptiva perstans, a form of cutaneous mastocytosis. A previous gastric biopsy was reevaluated, revealing two clusters (>15 mast cells; c-kit positive) of atypical mast cells with aberrant CD25 expression. These findings and a positive peripheral c-kit mutation (D816V) confirmed the diagnosis of SM. His decreased albumin and hepatomegaly classified his SM as the aggressive variant. Conclusion: This is a rare description of an undiagnosed systemic mastocytosis patient presenting with pericardial effusion/cardiac tamponade, likely due to pericarditis from mast cell mediators causing inflammation and subsequent effusion. This potentially life-threatening condition would be an important clinical presentation of SM.
O010 POST-NATAL MECHANISMS OF HUMAN HEMATOPOIETIC STEM CELL SELF-RENEWAL V. Bundy*, S. Sandoval, C. Seet, C. Parekh, C. Chin, C. He, Y. Zhu, L. Kohn, D. Rao, G. Crooks, Los Angeles, CA. Introduction: Hematopoietic stem cell (HSC) transplantation is the only potentially curative, non-experimental therapy available to treat severe primary immunodeficiency disease. Precise regulatory mechanisms to support and maintain HSCs remain to be elucidated. Micro RNAs (miRNAs) have been shown in many systems to regulate stem cell function. This study focuses on miRNA-specific mechanisms that support and maintain HSCs. Methods: Our laboratory has identified a genomic cluster of miRNAs (miR-99a/let-7c/miR-125b) that is highly coexpressed in hematopoietic stem cells, almost absent in progenitors and mature cells, with an expression pattern specific to postnatal hematopoiesis in the adult bone marrow. To determine the impact of increased miRNA expression in human HSCs, we generated lentiviral vectors to overexpress let-7c, miR-125b, or the entire cluster. Results: Lentiviral expression of let-7c alone decreased the number and frequency of CD34+ cells, reduced long-term culture initiation cells (LTC-ICs) and increased myeloid cell output. In contrast, expression of miR-125b alone expanded CD34+ cells and LTC-ICs. Expression of the entire miRNA cluster revealed a phenotype intermediate between let-7c and mir-125b overexpression. We have now also developed lentiviral “sponge” vectors to inhibit each miRNA individually, and hypothesize that inhibition of let-7c will enhance HSC proliferation due to un-opposed miR-125b. Conclusion: Our data suggests that let-7c may inhibit miR-125binduced proliferation during adult hematopoiesis. Our future goal is to use bioinformatics packages that combine miRNA and gene
expression analyses to identify molecular targets of let-7c and miR125b. We will use RNA-Seq to identify early transcriptional changes that occur after both over-expression and knockdown.
O011 IMMUNOGLOBULIN MANAGEMENT APPROACHES IN AMERICAN PATIENTS WITH COMMON VARIABLE IMMUNE DEFICIENCY AND AUTOIMMUNITY K. Kennedy*1, C. Cunningham-Rundles2, M. Morsheimer3, 1. Philadelphia, PA; 2. New York, NY; 3. Wilmington, DE. Introduction: Common variable immune deficiency (CVID) is a primary immune deficiency characterized by B cell dysfunction and paucity of protective specific antibodies. Autoimmunity, and commonly hematologic cytopenias, is also a manifestation. Immunoglobulin replacement therapy is the cornerstone of management; treatment route and dose can be used to modulate the frequency and severity of cytopenias. Typically IV immunoglobulin administration (IVIG) at high doses is required for immunomodulatory benefits, however international experience suggests subcutaneous administration at lower doses can also be successful. We aim to summarize the American experience regarding immunoglobulin route and dosing among CVID subjects with autoimmunity. Methods: A USIDNET enrollment characteristic query of 1494 CVID patients revealed 105 cases with autoimmunity. Variables assessed included sex, autoimmune disorder, transfusion history, adjunctive immunomodulatory medications, and immunoglobulin dose and administration route. STATA performed descriptive statistics. Results: The majority were female (61%) and treated with IVIG (72%). One third had cytopenias, most commonly immune thrombocytopenic purpura (14.2%). Nearly 80% with cytopenias received IVIG (300 to 1300 mg/kg/dose); 67% of these patients required immunomodulatory medications and 18% required transfusions. Approximately 20% with cytopenias were treated with subcutaneous immunoglobulin (SCIG) (100-150mg/kg/dose); 86% of these patients required immunomodulatory medications and 42% required transfusions. Conclusion: Most American CVID patients with cytopenias were managed with IVIG and had lower rates of immunomodulatory medications and transfusions than those on SCIG. There was a wide range of autoimmunity noted in the cohort with the same preference for IVIG noted for non-hematologic complications. Institutional-level data is required to identify characteristics predictive of success on SCIG.
O012 A SINGLE CENTER EXPERIENCE OF SCID NEWBORN SCREENING IN ILLINOIS J. Bergerson*, A. Skoskiewicz, R. Fuleihan, Chicago, IL. Background: Severe combined immunodeficiency (SCID) is primary immunodeficiency that result from the absence or diminished function of T cells. SCID is phenotypically classified by the presence or absence of B and NK cells and each subtype can be caused by defects in a number of different genes. Early diagnosis and prompt treatment of SCID leads to decreased patient mortality from disease complications. In May 2014, Illinois instituted newborn screening (NBS) of all infants for T-cell lymphopenia via Tcell receptor excision circle (TREC) assay. Methods: TREC level was performed as part of the Illinois state NBS program. Infants who had abnormal TREC levels (<300 in year one, and <250 in year two) were referred for further evaluation. Results: We identified patients with SCID, 22q11 deletion syndromes, Trisomy 21, and idiopathic T cell lymphopenia (iTCL) from all infants referred with low TREC levels. Since initiation of statewide newborn screening for SCID we evaluated six infants with absent TREC levels (TREC ¼ 0). Four of these six patients had typical SCID. The two remaining patients had iTCL. One of the patients
Abstracts: Oral Concurrent Sessions / Ann Allergy Asthma Immunol 117 (2016) S1eS21
diagnosed with iTCL has increasing T-cells and the other remains severely lymphopenic. Conclusions: Our data over two years of NBS in Illinois demonstrates that not all patients presenting with absent TREC levels have SCID. However, all of the patients with a diagnosis of SCID had TREC levels of zero. Therefore in our experience newborn screening can correctly identify those individuals with SCID or severe T cell lymphopenia, but additional testing is needed to confirm the diagnosis.
O013 NOVEL RAG-1 MUTATION IDENTIFIED IN A PATIENT WITH HYPOMORPHIC SEVERE COMBINED IMMUNODEFICIENCY (SCID) D. Arnold*, J. Heimall, Philadelphia, PA. Background: TREC newborn screening facilitates early diagnosis of both typical and hypomorphic SCID. Hypomorphic SCID patients often have abnormalities in RAG1/RAG2 enzymes. RAG1/RAG2 mediate the process of VDJ rearrangement in T and B cell progenitors, with defects leading to a T-B-NK+ SCID that can have a highly variable clinical presentation, including classic SCID, Omenn Syndrome and late-onset autoimmunity. Case Presentation: A newborn Caucasian female presented for evaluation due to low but not absent TRECs on state-based newborn screening. Immunology studies demonstrated: CD3 949, CD4 575, CD4/CD45RA 312, CD4/CD45RO 185, CD8 359, CD19 89, CD16/CD56 811; PHA proliferation 72004 CPM. This raised concern for hypomorphic SCID. Genetic testing demonstrated W204X and W522C mutations in the RAG1 gene. The W522C missense mutation has been reported previously in a patient with Omenn Syndrome. However, the W204X mutation has not previously been reported. It is predicted to cause loss of normal protein function through protein truncation. Thus, W204X was considered to be a disease-causing mutation. At 4 months of age, the patient received an unrelated umbilical cord blood transplant (UCB HSCT) following myeloablative conditioning. By 6 months post-transplant, immune studies demonstrated: CD3 1361, CD4 792, CD4/CD45RA 490, CD4/ CD45RO 354, CD8 509, CD19 1699, CD19/CD27/IgD- 23, CD16/CD56 907; PHA proliferation 69215 CPM. IgG was normal for age off IVIG. Engraftment is 100% across T, B and myeloid lineages. At 2.5 years of age, she is alive and well. Discussion: A novel RAG1 W204X mutation was demonstrated in this patient with hypomorphic SCID, who was successfully treated with UCB HSCT.
O014 SPLENOMEGALY AND IGA DEFICIENCY PREDICTS GRANULOMATOUS LYMPHOCYTIC INTERSTITIAL LUNG DISEASE (GLILD) IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) S. Hartono*1, M. Motosue2, S. Khan1, V. Rodriguez1, R. Divekar1, A. Joshi1, 1. Rochester, MN; 2. Honolulu, HI. Introduction: A subset of CVID patients develops granulomatous lymphocytic interstitial lung disease (GLILD), which is associated with early mortality. We sought to determine a set of clinical and laboratory parameters that correlate with GLILD development and progression. Methods: The study is a retrospective nested case (CVID subjects with GLILD)-control (CVID subjects without GLILD) chart review. Network and univariate analysis was used to identify clinical and laboratory parameters at the time of diagnosis that are associated with GLILD. Predictive accuracy of the identified variables was determined by logistic regression. Results: 26 cases with radiologic evidence of GLILD were included in this study. 18/26 (69%) of the cases had co-existent splenomegaly with lower IgA levels (p¼0.04) compared to the controls. Subjects with low IgA (<13 mg/dL) also had expansion of CD21low B cells
S5
(% CD21low >5) (p¼0.007). Univariate analysis revealed that splenomegaly (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.9 e 74.5), history of autoimmune cytopenia (OR 4.8, 95% CI 1.1 e 20.2), low IgA (OR 3.6, 95% CI 1.2 e 11.9), and expansion of CD21low (OR 5.8, 95% CI 1.6 e 24.7) were independently associated with GLILD. Logistic regression analysis showed that splenomegaly, history of cytopenia (ITP or AIHA), low IgA, and expansion of CD21low B cells are highly sensitive in predicting presence of GLILD (area under the receiver-operating curve of 0.86). Conclusion: Presence of splenomegaly, history of autoimmune cytopenia, low serum IgA, and expansion of CD21low B cells may be useful to identify a group of patients at high risk for development of GLILD.
Figure. Categorical data from abstracted dataset was converted to a bipartite network graph to reveal overview of associations. Incomplete variables were excluded to avoid bias. Gray nodes: GLILD, white nodes: no GLILD. Black squares: clinical variable.
O015 TOLERABILITY OF A NEW HUMAN IMMUNE GLOBULIN SUBCUTANEOUS, 20% PREPARATION IN PRIMARY IMMUNODEFICIENCY DISEASES S. Gupta*1, M. Stein2, I. Melamed3, I. Hussain4, K. Paris5, W. Engl6, B. McCoy7, C. Rabbat8, L. Yel7, 1. Irvine, CA; 2. North Palm Beach, FL; 3. Centennial, CO; 4. Tulsa, OK; 5. New Orleans, LA; 6. Vienna, Austria; 7. Cambridge, MA; 8. Bannockburn, IL. Introduction: Human immune globulin subcutaneous, 20% (SCIG 20%) is a ready-to-use, liquid preparation of highly purified human immunoglobulin G. Local adverse events (AEs) were investigated for potential association with increasing SCIG 20% infusion volumes and rates from a phase 2/3 study in patients with primary immunodeficiency diseases in North America. Methods: Patients received weekly SCIG 20% for up to w1.3 years. Up to 60 mL/site was administered. For patients weighing <40 kg, recommended infusion volumes were <¼20 mL/site (first two infusions) and then <¼60 mL/site (subsequent infusions), as tolerated. Recommended infusion rate for the first two infusions was 10-20 mL/hr/site; subsequent infusions could be increased <¼60 mL/hr/site, as tolerated. Results: Seventy-four patients aged 3-83 years received 4327 SCIG 20% infusions; 98.2% were not associated with a local adverse reaction. There was no association between increasing volume/site (30-39, 40-49, 50-59, and >¼60 mL/site) and causally-related local AE (0.4%, 1.4%, 1.1%, and 0.3%, respectively) rates. In all, 72% of patients reached 60 mL/hr/site, for a median total infusion time of 0.95 hr (53% and 85% of infusions were delivered in <1, and <1.5 hr, respectively). More than half (57%) of infusions were delivered at >¼60 mL/hr/site, with no association between the increasing infusion rates (30-39, 40-49, 50-59, and >¼60 mL/hr/site) and casually-related local AE (0.8%, 0.9%, 4.5%, and 0.4%, respectively)