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849 Granulomatous disease in common variable immunodeficiency — Not sarcoidosis
J ALLERGY CLIN IMMUNOL VOLUME 97, NUMBER 1, PART3
849
Granulomatous Disease in Common Variable
Abstracts
851
Antibody Deficiency with Normal Immunoglobuline P r e s e n t i n g in A d u l t L i f e . A Alshaar. MD. H Al-Assaly, biD, SJ McGeadv, MD, Phila., PA. The syndrome of antibody deficiency with normal immunoglobulins has been recognized for 30 years. These patients present in infancy with recurrent sinopulmonary pyogenic infections and are shown to have deficient antibody production to some antigens with otherwise intact immunity. We report 2 individuals who presented in mid life with findings of bronchiectasis and recurrent pyogenic infections. Evaluation revealed intact immune functioning except for antibody production: Patient I - Age 50 yrs. Patient II - Age 58 yrs. Baseline Post Stim Baseline Post Sam dT Titers Dipth Titer 1/3 1/9 1/9 1/27 Dipth Dilution 1+ 2+ 2+ 3+ Tetanus "liter 1/81 1/81 1/729 1/9 Tetanus Dilution 4+ 4+ 6+ 2+ These data indicate that the syndrome of antibody deficiency with normal immunoglobulins may occur as an acquired defect in mid life. In patients presenting with pyogenic pulmonary disease, evaluation of a panel of antibody synthesizing ability should be undertaken.
852
Agammaglobulinemia a s s o c i a t e d to c h r o m o s s o m e 2 d e l e t i o n . J Whaba MD; A Richieri-Costa MD; BT Costa-Carvalho MD; MMS Carneiro-Sampaio MD; D So16 MD', CK Nasnitz MD S~lo Paulo, Brazil
Immunodeficiency - - N o t S a r c o i d o s i s . LJ Meehani¢ MD. S Dikman MD. C Cunningham-Rundies MD PhD. New York, NY There have been patients described who have CVI and granulomatous lesions in lymphoid or solid organs. Such patients are often first diagnosed as having sarcoidosis instead of CVL From a total of 178 patients with CVI whose diagnosis was made by standard criteria, 14 were found to have biopsies that contained noncaseating granulomata in one or more locations. These patients ranged in age from 10 to 54, and 11 of the 14 were female. Three of the patients were black. Most of the patients had generalized lymphopenia, but a preserved ratio of helper to suppressor cells. In addition, 11 of the 14 patients had severely deficient T cell proliferation to PHA, ConA and PWM. Eight of our patients had been diagnosed as having sareoidosis at some time prior to the discovery of their hypogammaglobulinemia; :1 of 4 patients tested had increased ACE levels. Hepatosplenomegaly was present in all but 3 cases. Lymphadenopathy was found as well. Granulomata were found most often in the lungs, lymph nodes and liver. Autoimmune disease was also very common in this group; 3 patients had recurrent hemolytic anemia, 3 had a history of ITP, one patient had a history of Evan's syndrome, one had a history of rheumatoid arthritis and another had primary biliary cirrhosis. Despite standard treatment with intravenous immunoglobulin, these 14 patients have had a more complex clinical course than others. Two patients died of respiratory failure secondary to restrictive pulmonary disease and two patients are currently maintained on oxygen therapy for the same. Two patients have had granulomatous disease of the liver leading to cirrhosis. While one patient underwent splenectomy for hypersplenism, 4 were maintained on chronic corticosteroid therapy in order to avoid surgery. It is likely that the dysregulated T cell state is responsible for the granuloma formation in this subgroup of CVI patients. Not all patients with restrictive lung disease, splenomegaly and noncaseating granulomas have sarcoidosis.
850
Absence of Recurrent Bacterial Infections In Common Variable Immunodeficiency (CVID): Retention Of Functional A n t i b o d y R e s p o n s e s D e s p i t e S e v e r e P a n h y p o g a m m a g l o b u l i n e m i a . M Kalenian. MD and A I ~ , ME), U of Pem~3'lvania, Phila, PA CVID is characterized by severe hypogammaglobolinemia and recurrent bacterial infections of the upper and lower respiratory trees. Rarely, and inexplicably, CV1D patients do not experience recurrent bacterial infections. Such is the case with a 25 y o patient who was noted to have a markedly reduced serum globulin (1.6 g/dl; nl, 2.5-3.0 g/dl) during a routine evaluation at age 15 yrs. Ten years later, she was found to have an IgG of 81, IgA of, 8, and an IgM of 10 mg/dl. Her history was notable for the absence of recurrent sinusitis, otitis media, or pneumonia. She had no clinical evidence of protein loss and her serum albuntin was 4.5 g/dl. Her physical exam was normal. She had a normal C3, (24 and CH50. Delayed hypersensitivity skin tests were positive to mumps and tetanus toxoid. Flow cytometry analysis of her peripheral blood lymphocytes revealed a normal distribution of T and and B cell markers except for an increased percentage of cells expressing CD20 (19%). Despite her severe panbypogammaglobulinemia, she had normal IgG anti-mumps titers (immunized to mumps in 1994) and normal IgG booster antibody responses to tetanus toxoid and conjugated hemophilus influenza vaccines. She had a markedly impaired antibody response to pneumovax. She remains healthy after a further one year follow-up period without therapeutic intervention. Thus, in CV1, functional antibody responses may paradoxically be intact in the face of severe panhypogammaglobulinemia. We hypothesize that the presence of such functional antibody responses explains the benign course observed in these unusual CVI patients.
395
Deletions on chromossome 2 are rare and are usually observed as pan of a more complex duplication s3~adrome among progeny of balanced reciprocal translocation carriers. Association with immunodeficiency has not been described before, We report a 20 year-old male patient with facial anomalies, mental retardation and history of recurrent respiratory infections (otitis and pneumonias) since 2 years of age. Crohn's disease and immunedeficiency were diagnosed when he was 19 year-old. Parents are not consanguineous and he has two healthy brothers. There are no other cases in the family. Laboratory tests at the age of 19 years : IgM= < 7 mg/di; IgG = 66 mg/di; IgA= < 3 mg/dl; isohemmaglutinins and antipoliovirus antibodies were undetectable; CH50 = normal; TCD3 += 1953 cells/pl', T-CIM+= 777 cells/lal; T-CD8+ = 1155 cells/ixl; B-CDI9 ÷= 42 cells/M; PHA lymphoprohferative response was similar to a normal control. Karyotypo: 46,XY,del(2)(q32q33). The immunelectrophoresis showed low IgG levels, but both ~ and K chains were present. The patient was treated with sulfasalazine and intravenous gammaglobnlin with good response. Since this association was not reported before, more extensive study is necessary to elucidate whether the observed deletion is responsible for the immuandeficiency
849
Granulomatous Disease in Common Variable
Abstracts
851
Antibody Deficiency with Normal Immunoglobuline P r e s e n t i n g in A d u l t L i f e . A Alshaar. MD. H Al-Assaly, biD, SJ McGeadv, MD, Phila., PA. The syndrome of antibody deficiency with normal immunoglobulins has been recognized for 30 years. These patients present in infancy with recurrent sinopulmonary pyogenic infections and are shown to have deficient antibody production to some antigens with otherwise intact immunity. We report 2 individuals who presented in mid life with findings of bronchiectasis and recurrent pyogenic infections. Evaluation revealed intact immune functioning except for antibody production: Patient I - Age 50 yrs. Patient II - Age 58 yrs. Baseline Post Stim Baseline Post Sam dT Titers Dipth Titer 1/3 1/9 1/9 1/27 Dipth Dilution 1+ 2+ 2+ 3+ Tetanus "liter 1/81 1/81 1/729 1/9 Tetanus Dilution 4+ 4+ 6+ 2+ These data indicate that the syndrome of antibody deficiency with normal immunoglobulins may occur as an acquired defect in mid life. In patients presenting with pyogenic pulmonary disease, evaluation of a panel of antibody synthesizing ability should be undertaken.
852
Agammaglobulinemia a s s o c i a t e d to c h r o m o s s o m e 2 d e l e t i o n . J Whaba MD; A Richieri-Costa MD; BT Costa-Carvalho MD; MMS Carneiro-Sampaio MD; D So16 MD', CK Nasnitz MD S~lo Paulo, Brazil
Immunodeficiency - - N o t S a r c o i d o s i s . LJ Meehani¢ MD. S Dikman MD. C Cunningham-Rundies MD PhD. New York, NY There have been patients described who have CVI and granulomatous lesions in lymphoid or solid organs. Such patients are often first diagnosed as having sarcoidosis instead of CVL From a total of 178 patients with CVI whose diagnosis was made by standard criteria, 14 were found to have biopsies that contained noncaseating granulomata in one or more locations. These patients ranged in age from 10 to 54, and 11 of the 14 were female. Three of the patients were black. Most of the patients had generalized lymphopenia, but a preserved ratio of helper to suppressor cells. In addition, 11 of the 14 patients had severely deficient T cell proliferation to PHA, ConA and PWM. Eight of our patients had been diagnosed as having sareoidosis at some time prior to the discovery of their hypogammaglobulinemia; :1 of 4 patients tested had increased ACE levels. Hepatosplenomegaly was present in all but 3 cases. Lymphadenopathy was found as well. Granulomata were found most often in the lungs, lymph nodes and liver. Autoimmune disease was also very common in this group; 3 patients had recurrent hemolytic anemia, 3 had a history of ITP, one patient had a history of Evan's syndrome, one had a history of rheumatoid arthritis and another had primary biliary cirrhosis. Despite standard treatment with intravenous immunoglobulin, these 14 patients have had a more complex clinical course than others. Two patients died of respiratory failure secondary to restrictive pulmonary disease and two patients are currently maintained on oxygen therapy for the same. Two patients have had granulomatous disease of the liver leading to cirrhosis. While one patient underwent splenectomy for hypersplenism, 4 were maintained on chronic corticosteroid therapy in order to avoid surgery. It is likely that the dysregulated T cell state is responsible for the granuloma formation in this subgroup of CVI patients. Not all patients with restrictive lung disease, splenomegaly and noncaseating granulomas have sarcoidosis.
850
Absence of Recurrent Bacterial Infections In Common Variable Immunodeficiency (CVID): Retention Of Functional A n t i b o d y R e s p o n s e s D e s p i t e S e v e r e P a n h y p o g a m m a g l o b u l i n e m i a . M Kalenian. MD and A I ~ , ME), U of Pem~3'lvania, Phila, PA CVID is characterized by severe hypogammaglobolinemia and recurrent bacterial infections of the upper and lower respiratory trees. Rarely, and inexplicably, CV1D patients do not experience recurrent bacterial infections. Such is the case with a 25 y o patient who was noted to have a markedly reduced serum globulin (1.6 g/dl; nl, 2.5-3.0 g/dl) during a routine evaluation at age 15 yrs. Ten years later, she was found to have an IgG of 81, IgA of, 8, and an IgM of 10 mg/dl. Her history was notable for the absence of recurrent sinusitis, otitis media, or pneumonia. She had no clinical evidence of protein loss and her serum albuntin was 4.5 g/dl. Her physical exam was normal. She had a normal C3, (24 and CH50. Delayed hypersensitivity skin tests were positive to mumps and tetanus toxoid. Flow cytometry analysis of her peripheral blood lymphocytes revealed a normal distribution of T and and B cell markers except for an increased percentage of cells expressing CD20 (19%). Despite her severe panbypogammaglobulinemia, she had normal IgG anti-mumps titers (immunized to mumps in 1994) and normal IgG booster antibody responses to tetanus toxoid and conjugated hemophilus influenza vaccines. She had a markedly impaired antibody response to pneumovax. She remains healthy after a further one year follow-up period without therapeutic intervention. Thus, in CV1, functional antibody responses may paradoxically be intact in the face of severe panhypogammaglobulinemia. We hypothesize that the presence of such functional antibody responses explains the benign course observed in these unusual CVI patients.
395
Deletions on chromossome 2 are rare and are usually observed as pan of a more complex duplication s3~adrome among progeny of balanced reciprocal translocation carriers. Association with immunodeficiency has not been described before, We report a 20 year-old male patient with facial anomalies, mental retardation and history of recurrent respiratory infections (otitis and pneumonias) since 2 years of age. Crohn's disease and immunedeficiency were diagnosed when he was 19 year-old. Parents are not consanguineous and he has two healthy brothers. There are no other cases in the family. Laboratory tests at the age of 19 years : IgM= < 7 mg/di; IgG = 66 mg/di; IgA= < 3 mg/dl; isohemmaglutinins and antipoliovirus antibodies were undetectable; CH50 = normal; TCD3 += 1953 cells/pl', T-CIM+= 777 cells/lal; T-CD8+ = 1155 cells/ixl; B-CDI9 ÷= 42 cells/M; PHA lymphoprohferative response was similar to a normal control. Karyotypo: 46,XY,del(2)(q32q33). The immunelectrophoresis showed low IgG levels, but both ~ and K chains were present. The patient was treated with sulfasalazine and intravenous gammaglobnlin with good response. Since this association was not reported before, more extensive study is necessary to elucidate whether the observed deletion is responsible for the immuandeficiency