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IgA and IgG Subclass Deficiencies Treatment & Management

  • Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Aug 15, 2014
 

Medical Care

As noted in Medication, even if the patient cannot produce specific antibodies, the decision to treat with intravenous immunoglobulin (IVIg) is controversial. Aggressive use of antibiotics is required for recurrent respiratory tract infections, such as sinusitis, asthma, and bronchitis.

The use of prophylactic antibiotics (eg, during the winter months) has not been well studied but can be considered. Cohort studies indicate that this approach can be successful.[50] If conventional initial intervention with antibiotics is not successful, a trial of IVIg at 400-600 mg/kg for 6 months may be considered. For partial deficiencies (ie, specific antibody deficiency), IVIg can be stopped if no clinical response is observed.

In IgG subclass deficiency, most clinicians reserve IVIg for patients unable to make antibodies to both protein and polysaccharide antigens. Although reports mention a possible beneficial effect of decreased duration of bacterial infection in patients with IgG subclass deficiency,[51] an unpublished, blinded, and randomized trial of IVIg in IgG subclass deficiency showed that IVIg was not effective. However, cohort studies indicate a benefit, especially in those patients with fewer responses to pneumococcal polysaccharide challenge.[31]

Some advocate using IVIg if a patient aged 3 years or older does not respond to the unconjugated vaccine, especially if the titer or quantity to any 1 serotype (eg, type 3 polysaccharide, the most immunogenic) does not increase 2-fold.

Patients with a decreased ability to make antipolysaccharide antibodies should be immunized with polysaccharide-protein conjugate vaccines, such as H influenzae type b (HIB) with diphtheria-tetanus. The conjugated protein allows anti-HIB antibodies to develop, though 2 or 3 doses are usually required.

A conjugated pneumococcal vaccine is now licensed for use in the United States. Conjugated meningococcal vaccine (Menactra) is also now yet available in the United States. Sorensen et al (1998) showed that a significant percentage of children with specific antibody deficiency develop protective antibody levels to the conjugated pneumococcal vaccine (Prevnar) with a subsequently decreased rate of infections.[52] Patients with isolated IgG3 subclass deficiency have a similar dilemma as to whether IVIg is helpful.[53]

OM-85 BV has been used in Europe for over 20 years to stimulate mucosa-associated lymphoid tissue and up-regulate the TH-1 response. One study did not find any increased induction of autoantibodies in IgA-deficient patients.[54] The authors did not comment on any beneficial effect in these patients. More specific therapy may become available if clinical studies on interleukin 21 confirm potential therapy in patients with common variable and selective IgA deficiencies.[55]

Aggressive treatment of underlying allergies and/or asthma may help reduce the frequency and/or severity of recurrent respiratory tract infections, such as sinusitis and bronchitis.

Conventionally treat associated autoimmune diseases. Nothing indicates that patients with a concomitant specific IgA deficiency do worse than those without any immunodeficiency.

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Surgical Care

A few patients with chronic upper or lower respiratory infections and subsequent structural changes may need strategic, long-term, broad-spectrum antibiotics, in addition to chest physiotherapy and sinus surgery.

Although many patients benefit from the placement of tympanostomy tubes to manage recurrent otitis media and/or they might undergo endoscopic sinus surgery for chronic sinusitis, the importance of aggressive medical therapy for the underlying immunodeficiency and its accompanied allergic condition cannot be overemphasized.

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Consultations

Consultation with a surgeon may be needed for patients with chronic infections of the upper or lower respiratory tracts. Chronic sinusitis may require various ear, nose, and throat (ENT) procedures to promote drainage.

A rheumatologist, allergist/immunologist, or both may be required because of the various autoimmune and allergic diseases present with increased frequency in B-cell disorders.

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Diet

Gluten-free and other restricted diets have been tried but are ineffective in these disorders when chronic diarrhea is present.

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Activity

Encourage normal activity.

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Contributor Information and Disclosures
Author

Terry W Chin, MD, PhD Associate Clinical Professor, Department of Pediatrics, University of California, Irvine, School of Medicine; Associate Director, Cystic Fibrosis Center, Attending Staff Physician, Department of Pediatric Pulmonology, Allergy, and Immunology, Memorial Miller Children's Hospital

Terry W Chin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American College of Chest Physicians, American Federation for Clinical Research, American Thoracic Society, California Society of Allergy, Asthma and Immunology, California Thoracic Society, Clinical Immunology Society, Los Angeles Pediatric Society, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Acknowledgements

John Wilson Georgitis, MD Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

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Table. Immune Globulin, Intravenous [56, 57, 58, 59]
Brand(Manufacturer) Manufacturing Process pH Additives (IVIg products containing sucrose are most often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs]) Parenteral Form and Final Concentrations IgA Content mcg/mL
Carimune NF



(CSL Behring)



Kistler-Nitschmann fractionation; pH 4, nanofiltration 6.4-6.8 6% solution: 10% sucrose, < 20 mg NaCl/g protein Lyophilized powder 3%, 6%, 9%, 12% Trace
Flebogamma



(Grifols USA)



Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization 5.1-6 Sucrose free, contains 5% D-sorbitol Liquid 5% < 50
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.1 0.25M glycine Ready-for-use Liquid 10% 37
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation 4-4.5 Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycine Liquid 10% 46
Gammaplex



(Bio Products)



Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation 4.8-5.1 Contains sorbitol (40 mg/mL); do not administer if fructose intolerant Ready-for-use solution 5% < 10
Iveegam EN



(Baxter Bioscience)



Cohn-Oncley fraction II/III; ultrafiltration; pasteurization 6.4-7.2 5% solution: 5% glucose, 0.3% NaCl Lyophilized powder 5% < 10
Polygam S/D



Gammagard S/D



(Baxter Bioscience for the American Red Cross)



Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated 6.4-7.2 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose Lyophilized powder 5%, 10% < 1.6 (5% solution)
Octagam



(Octapharma USA)



9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events



Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization 5.1-6 10% maltose Liquid 5% 200
Panglobulin



(Swiss Red Cross for the American Red Cross)



Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration 6.6 Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl Lyophilized powder 3%, 6%, 9%, 12% 720
Privigen Liquid 10%



(CSL Behring)



Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration 4.6-5 L-proline (approximately 250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose) Ready-for use liquid 10% < 25
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