Antibody Deficiency-Newborn Screening-Immunodeficiency-Antibody Titers-Allergists

Immunodeficiency - Twitter summary from 2012 #AAAAI meeting

This summary was compiled from the tweets posted by the following allergists/immunologists who attended the 2012 annual meeting of the The American Academy of Allergy Asthma and Immunology (AAAAI): Dr. Melinda Rathkopf ?@mrathkopf, Nathaniel Hare M.D. ?@DrNathanHare and Yesim Y Demirdag ? @DrYesimDem. The tweets were labeled #AAAAI. The text was edited and modified by me.
Immunodeficiency
Dr Tom Fleisher on flow cytometry: useful in PIDD for diagnostic work up, assessment for biologic effect and functional testing.
How to evaluate cell med immunity in kids: start with quantitative first, then move on to functional evaluation if the child is small (there is an issue with the amount of blodd needed).
T cell functional studies include: mitogens, recall antigens, alloantigens. Pha and Con-A are T cell mitogens. Pokeweed is a T-cell-dependent B-cell mitogen.
The amount of oxidative burst is related to morbidity in CGD.
T cell receptor excision circles (TRECs)
The target condition for newborn screening for PIDD is SCID. Secondary conditions are other PIDD with lymphopenia. Other conditions that may be picked up by NBS for SCID include chylothorax, Jacobsen syndrome, cartilage hair hypoplasia, trisomy 21.
Initially, SCID prevalence was thought to be 1 in 100,000, but now after the preliminary data from NBS it is about 1 in 40,000.
Newborn screening for T cell developmental defects implicated in SCID includes TRECs (T cell receptor excision circles). TRECs occur during thymic T cell receptor rearrangement. Naive T cells demonstrate TRECs, memory T cells do not.
Quantitative PCR detects frequency of TRECs. Four U.S. states use TRECs for SCID screening currently, more to follow. More than 10 states are in the process of starting newborn screening for SCID.
If the first DBS (dry blood spot) PCR for TRECs is abnormal, repeat it from the same blood spot with a control gene PCR (beta actin).
Severe combined immunodeficiency (SCID) - 4 groups according to T/B/NK cells (click to enlarge the image).
Approach to evaluation of PIDD in adults
The approach to the evaluation of PIDD in adults was discussed by Drs. Joyce Yu and Zuhair Ballas:
The most common cause of immune deficiency is secondary, not PIDD. PIDD presentation is more subtle in adults than kids. Think about unusual: infection/ organism, duration, complication, failure to thrive in adults. Then consider immune evaluation.
If there is poor wound healing, dentures at early age, wound dehiscence - check the immune system.
Consider medications and malignancy, in patients with rec infections. Immunosuppressants and chemotherapy can easily cause problems. Antipeliptics can cause hypogammaglobulinemia. Tegretol is the only antiseizure medication that is not yet associated with hypogammaglobulinemia.
Rituximab (anti-CD20) is used for autoimmune diseases such as ITP. B cells are wiped out with anti-CD20 and may take 6 months to recover. Plasma cells are long-lived. Pt on rituximab have normal IgG and IgA but low IgM. Rituximab patients don't make new antibodies, but old antibody titers are not generally affected.
Pneumococcal titers
Typically, adults respond to Pneumovax until age 85. A subset of patients only have temporary polysaccharide response, so if concerned about the patient, follow the antibody titers.
Pediatric patients: check pneumococcal titers for serotypes to Prevnar.
Adult patients: high pneumococcal titers may not be truly protective. For example, with HIV there are high antibody titers, but as CD4 cell count drops, they can't make new antibodies.
Pneumococcal titers: if pre-immunization titers are above 5, the patient is not likely to respond for those serotypes.
The consensus is that 50% response in kids, and 70% response in adults to Pneumovax is considered normal.
Specific antibody deficiency with normal immunoglobulin lev read more..