Primary immunodeficiencies - Twitter summary from 2013 #AAAAI meeting

This summary was compiled from the tweets posted by allergists/immunologists who attended the 2013 annual meeting of the American Academy of Allergy Asthma and Immunology (AAAAI) (see the list at the end). The tweets were labeled #AAAAI. The text was edited and modified by me.

Dr. Lisa Filipovich presented on "New insights and opportunities in curative therapies for primary immunodeficiency".

From @IgECPD: “For the uninitiated Immunology is a series of colourful circles on a white background labeled with capital letters/numbers, linked by arrows”.

The first successful allogenic bone marrow transplant for SCID was almost 44 years ago. Over 150 primary immunodeficiencies (PIDs) currently recognized. More than 120 genes are linked to PIDs; many PIDs are prematurely lethal and deserve curative treatment such as BMT or gene therapy.

Dr Bonilla: according to 2011 WHO/IUIS classification there are 181 PIDs, with many unknown genetic defects. There are probably about 1250 PIDs according to Dr Bonilla's calculation. Dr. Bonilla: Theoretical estimate of total number of primary immunodeficiency disorders (PIDs) around 1250

It is important to diagnosis SCID early to provide protective isolation, avoid live vaccines, and allow time to optimally plan the BMT.

Primary immunodeficiency disorders (PIDD) (click to enlarge the image).

Diagnosis of PIDs

TRECs for diagnosis

Population based Newborn screening program (NBS) for SCID via TRECs has been very successful. Newborn screening for SCID is now available in 50% of US states. Head of HHS has been pushing for more.

A prospective SCID study is underway. 50% were discovered because of newborn screening or family history. Diagnosis at 15 days vs 181 days.

Adding KRECs to NBS for SCID (TRECs) will help detect B cell defects as well as determining SCID subtypes. Explanation of abbreviations: kappa-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs).

Whole Exome Sequencing (WES)

Whole Exome Sequencing (WES) is used in diagnosing PIDs. Cost of WES ranges between $1,300 an $1,700. WES sequences only known exomes, and it cannot sequence certain genes (highly polymorphic genes such as MHC).

Whole exome sequencing can be useful for diagnosis of patients with undiagnosed PIDs. Costs decreasing rapidly over time. Whole exome sequencing requires time-intensive post-sequencing analysis - this is the main barrier to quick turnaround.

Dr Jack Routes: New screening for 22q11.2 microdeletion (DiGeorge) syndrome employs qRT-PCR for copy number variations in TBX1 gene.

Newborn screening for SCID will benefit from new advances in WES/iPS technology, especially for rare/novel disorders.

A sad case: A 22q patient developed VZV pneumonia after routine 12-month vaccines. CD3 count was 400 when checked later. Remember to report vaccine reactions to VAERS for confirmatory testing, documentation, and patient compensation fund access.


However, there is less than a 25% chance of finding a matched sibling donor for BMT - national marrow donor program critical to enhance this process. "BMDW" - bone marrow donors worldwide - is a database of over 50K donors that HCP can search for matches. Not surprisingly, outcomes are superior with HLA-identical sibling donors compared to unrelated haploidentical donors.

Gene therapy

Gene therapy for SCID and other PIDs has been challenging; now starting to look safer and more promising.

Antibody deficiency

The delay in diagnosis of patients with antibody deficiency is up to 20 yrs (average is 8 yrs).

Assessment of T cell independent response should wait until the child completes routine immunizations (approximately 18 months).

Response to vaccines

A protective level is equal or greater than 1.3. A positive response is there if it goes from unprotected level to protected level.

A protective response to each pneumococcal vaccine is 1.3 mcg/ml or higher. The rise for each pneumococcal serotypes varies by age and by serotype.

Source: JACI Sept 2012:130:S1-S24 - Working group report on use of vaccine response in dx of immune deficiency.

There is a screening available for high risk patients (ENT, Pulmonology, A/I pts) for immunoglobulin deficiency on a dry blood spot (developed by Quest lab). It needs only 10-30 mcl blood. Dry blood spot QuIg analysis correlates with whole blood analysis.

April 25 is Primary Immunodeficiency Day. Visit


Dr Tony Bonilla: Known gene defects in CVID account for very tiny fraction (less than 5%) of total CVID cases. GWAS in CVID yielded numerous candidate genes, but few were confirmed as of late as playing direct causal role (JACI 2011).

CVID is a truly heterogeneous disorder. Better definitions are needed for subgroup stratification.

Decreased switched-memory (CD27+/IgD-/IgM-) B-cells are found in numerous PIDs; NOT exclusive to, or diagnostic of CVID. Diagnosis of CVID can NOT be made by B-cell phenotyping alone.

Dr Warnatz: Naive t-cell measurements should be a routine component of screening in patients with CVID; defects are commonly seen.

Patients with CVID have increased CD20-mediated BCR internalization, and subsequent hyporesponsiveness.


Primary immunodeficiencies in patients with recurrent ENT infections. JACI 2013.

Allergists are on Twitter - follow them

Allergists increased Twitter use 470% in one year - 25 allergists reached 250,000 individuals from the 2012 #AAAAI meeting (see the references here). This summary was compiled from some of the tweets posted by the following allergists:

This is a list of the allergists who used Twitter to post updates from the 2013 #AAAAI meeting. The list is open for edit, please feel free to add your own info.

I would strongly encourage you to post updates on Twitter from the CME conferences that you are planning to attend in the future. Here is how to do it: Twitter for Physicians: How to use Twitter to keep track of the latest news and scientific meetings, and share information with colleagues and patients.

Disclaimer: The text was edited, modified, and added to by me. This is one of a series of posts that will be published during the next few weeks.

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