Ann Allergy Asthma Immunol xxx (2015) 1e2
Contents lists available at ScienceDirect
Letter
Hypogammaglobulinemia with normal antibody response progressing to common variable immunodeficiency
This report describes 3 adult patients who presented with recurrent infections, hypogammaglobulinemia, and a normal pneumococcal antibody response that evolved to fulfill criteria for common variable immunodeficiency (CVID) over a course of 1 to 3 years. Diagnosis of CVID is based on decreased levels of total IgG, IgA, and/or IgM and a deficiency in specific antibody production.1e3 Specific antibody deficiency is characterized by normal levels of IgG, IgA, and IgM but abnormal IgG antibody responses to polysaccharide vaccines.3,4 Occasionally, patients are seen with a low IgG level but with a normal antibody response, with no apparent cause for the low IgG level. Our hypothesis is that some of these patients could represent an early manifestation of CVID and could lose their antibody function over time. Three patients presented with a clinical picture suggestive of CVID but did not fulfill the criteria for that diagnosis because they had a low IgG level but normal antibody function. Protein loss as a cause of hypogammaglobulinemia was excluded. All patients initially had protective antibody titers (>1.3 mg/mL) to more than 70% of pneumococcal serotypes. Follow-up testing showed fewer than 70% of serotypes in the protective range and continued to demonstrate IgG levels 2 SDs below normal, thus fulfilling World Health Organization criteria for CVID.5 Pneumococcal IgG titers were measured by Quantitative Multiplex Bead Assay (ARUP Laboratories, Salt Lake City, Utah). Patient A was a 24-year-old white woman with recurrent infections since 16 years of age, including upper respiratory infections, otitis media, bronchitis, thrush, folliculitis, urinary tract infections, oral herpes simplex virus ulcers, and vaginal yeast infections. In 2006, her IgG, IgA, and IgM levels were 592, 29, and 53 mg/dL, respectively (normal ranges: IgG 700e1,600 mg/dL, IgA 70e400 mg/dL, IgM 40e230 mg/dL); her postimmunization titers to 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) were protective in 93% of serotypes (13 of 14). IgG isohemagglutinin anti-B titer was lower than 2. IgG titers to diphtheria and tetanus were 2.63 and 8.73 IU/mL, respectively. Flow cytometry showed normal numbers of T, B, and natural killer cells. She was not on medications associated with hypogammaglobulinemia. In 2008, IgG, IgA, and IgM levels were 414, 24, 39 mg/dL, respectively, and postimmunization titers to PPV23 were protective in 36% of serotypes (5 of 14; Fig 1). Patient B was a 46-year-old white woman with a 10-year history of recurrent rhinosinusitis, pneumonia, “shingles,” and an unknown type of vaginitis while on antibiotics. In 2011, her IgG, IgA, and IgM levels were 644, 69, and 198 mg/dL, respectively; random Disclosure: Authors have nothing to disclose.
titers to PPV23 were protective in 72% of serotypes (10 of 14). Diphtheria and tetanus IgG levels were 0.06 and 3.97 IU/mL respectively. She had normal numbers of T, B, and natural killer cells. In 2012, her IgG, IgA, and IgM levels were 320, 69, and 111 mg/ dL, respectively. Random pneumococcal titers were protective in 52% of serotypes (12 of 23). Anti-B IgG titer was lower than 2. Diphtheria and tetanus IgG levels were 2.63 and 8.73 IU/mL, respectively. In 1 year, protective pneumococcal titers decreased (from 71% to 52%). She was not on any medications associated with hypogammaglobulinemia. Patient C was a 38-year-old white woman with asthma and chronic obstructive pulmonary disease who presented with recurrent rhinosinusitis, bronchitis, candida esophagitis, and chronic diarrhea. In 2004, her IgG, IgA, and IgM levels were 349, 210, and 129 mg/dL, respectively; postimmunization titers were protective in 71% of pneumococcal serotypes. Diphtheria and tetanus IgG levels increased from 0.27 and 3.47 IU/mL to 2.42 and higher than 20.05 IU/mL after vaccination, respectively. Anti-B IgG titer was higher than 64; anti-A IgG was 32. In 2007, her IgG, IgA, and IgM levels were 185, 302, and 98 mg/dL, respectively. Postimmunization titers to PPV23 were protective in 43% of serotypes (6 of 14). She did not have earlier monitoring of her antibody response owing to lack of regular follow-up. She was on intermittent prednisone when pneumococcal response was evaluated. In 2004, she was on 40 mg of prednisone daily before immunization, tapered by 5 mg weekly until she was on 20 mg at immunization. She was not on other immunosuppressive medications. In 2007, she was on 10 mg of prednisone daily. The IgG fluctuation might have been due to changes in her prednisone dose; however, IgA and IgM levels fluctuated in synchrony with IgG, making this possibility unlikely. In summary, 3 patients presented with recurrent infections, hypogammaglobulinemia, and normal pneumococcal antibody response that evolved over a short period (
Contents lists available at ScienceDirect
Letter
Hypogammaglobulinemia with normal antibody response progressing to common variable immunodeficiency
This report describes 3 adult patients who presented with recurrent infections, hypogammaglobulinemia, and a normal pneumococcal antibody response that evolved to fulfill criteria for common variable immunodeficiency (CVID) over a course of 1 to 3 years. Diagnosis of CVID is based on decreased levels of total IgG, IgA, and/or IgM and a deficiency in specific antibody production.1e3 Specific antibody deficiency is characterized by normal levels of IgG, IgA, and IgM but abnormal IgG antibody responses to polysaccharide vaccines.3,4 Occasionally, patients are seen with a low IgG level but with a normal antibody response, with no apparent cause for the low IgG level. Our hypothesis is that some of these patients could represent an early manifestation of CVID and could lose their antibody function over time. Three patients presented with a clinical picture suggestive of CVID but did not fulfill the criteria for that diagnosis because they had a low IgG level but normal antibody function. Protein loss as a cause of hypogammaglobulinemia was excluded. All patients initially had protective antibody titers (>1.3 mg/mL) to more than 70% of pneumococcal serotypes. Follow-up testing showed fewer than 70% of serotypes in the protective range and continued to demonstrate IgG levels 2 SDs below normal, thus fulfilling World Health Organization criteria for CVID.5 Pneumococcal IgG titers were measured by Quantitative Multiplex Bead Assay (ARUP Laboratories, Salt Lake City, Utah). Patient A was a 24-year-old white woman with recurrent infections since 16 years of age, including upper respiratory infections, otitis media, bronchitis, thrush, folliculitis, urinary tract infections, oral herpes simplex virus ulcers, and vaginal yeast infections. In 2006, her IgG, IgA, and IgM levels were 592, 29, and 53 mg/dL, respectively (normal ranges: IgG 700e1,600 mg/dL, IgA 70e400 mg/dL, IgM 40e230 mg/dL); her postimmunization titers to 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) were protective in 93% of serotypes (13 of 14). IgG isohemagglutinin anti-B titer was lower than 2. IgG titers to diphtheria and tetanus were 2.63 and 8.73 IU/mL, respectively. Flow cytometry showed normal numbers of T, B, and natural killer cells. She was not on medications associated with hypogammaglobulinemia. In 2008, IgG, IgA, and IgM levels were 414, 24, 39 mg/dL, respectively, and postimmunization titers to PPV23 were protective in 36% of serotypes (5 of 14; Fig 1). Patient B was a 46-year-old white woman with a 10-year history of recurrent rhinosinusitis, pneumonia, “shingles,” and an unknown type of vaginitis while on antibiotics. In 2011, her IgG, IgA, and IgM levels were 644, 69, and 198 mg/dL, respectively; random Disclosure: Authors have nothing to disclose.
titers to PPV23 were protective in 72% of serotypes (10 of 14). Diphtheria and tetanus IgG levels were 0.06 and 3.97 IU/mL respectively. She had normal numbers of T, B, and natural killer cells. In 2012, her IgG, IgA, and IgM levels were 320, 69, and 111 mg/ dL, respectively. Random pneumococcal titers were protective in 52% of serotypes (12 of 23). Anti-B IgG titer was lower than 2. Diphtheria and tetanus IgG levels were 2.63 and 8.73 IU/mL, respectively. In 1 year, protective pneumococcal titers decreased (from 71% to 52%). She was not on any medications associated with hypogammaglobulinemia. Patient C was a 38-year-old white woman with asthma and chronic obstructive pulmonary disease who presented with recurrent rhinosinusitis, bronchitis, candida esophagitis, and chronic diarrhea. In 2004, her IgG, IgA, and IgM levels were 349, 210, and 129 mg/dL, respectively; postimmunization titers were protective in 71% of pneumococcal serotypes. Diphtheria and tetanus IgG levels increased from 0.27 and 3.47 IU/mL to 2.42 and higher than 20.05 IU/mL after vaccination, respectively. Anti-B IgG titer was higher than 64; anti-A IgG was 32. In 2007, her IgG, IgA, and IgM levels were 185, 302, and 98 mg/dL, respectively. Postimmunization titers to PPV23 were protective in 43% of serotypes (6 of 14). She did not have earlier monitoring of her antibody response owing to lack of regular follow-up. She was on intermittent prednisone when pneumococcal response was evaluated. In 2004, she was on 40 mg of prednisone daily before immunization, tapered by 5 mg weekly until she was on 20 mg at immunization. She was not on other immunosuppressive medications. In 2007, she was on 10 mg of prednisone daily. The IgG fluctuation might have been due to changes in her prednisone dose; however, IgA and IgM levels fluctuated in synchrony with IgG, making this possibility unlikely. In summary, 3 patients presented with recurrent infections, hypogammaglobulinemia, and normal pneumococcal antibody response that evolved over a short period (
