[CIS PIDD] [cis-pidd] B-cell memory subsets & Selective IgG deficiency

Thu Feb 16 17:12:21 EST 2017

Dear Mikko,

Thank you so much for your suggestions and for providing the very useful reference on age and naïve B-cells. I’m really grateful for your responses which are always very helpful!
We excluded myeloma on SPEP, serum free light chain assay, and urine bence jones light chains. I have not yet done bone marrow or CT scans to exclude MDS and lymphoma.

I just wonder about the functional significance of low naïve B-cells in terms of susceptibility to infections? Is this again a problem of blood representing just 1% of lymphocytes with the problem of not knowing the make up of B-cells in lymphoid tissue? How robust do people find measurements of B-cell memory subsets, and is there a useful QC that can be used (like for immune subsets on flow: T-cells,  B-cells + NK must add up to 100, and CD4 + CD8 must be within 10% of CD3 or else check for increased gamma deltoids).

I’d really appreciate hearing any feedback about this.

Many thanks for always being so generous in sharing your experience.

All the best,

Stan

From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Thursday, 16 February 2017 at 7:25 AM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] B-cell memory subsets & Selective IgG deficiency

Hi Stan

one really would need serotype specific responses... Especially in a case like 1. If you have the pre-post-vaccination serums, send somewhere?

There are numerous immunologic diseases (not all PID) where low smBs have been found. Thus that alone is very unspecific. However, 0% seems low indeed.

As to the low naives, I would love to hear also others to comment.
Often steroid-induced in adults (but then memory Bs abundant). And long-term gcs often lower IgG levels. Klaus?

Age is a factor in naive B cells:
Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging.
de Bourcy CF, et al. Proc Natl Acad Sci U S A. 2017.
The one you describe 1,16%) is however extreme. Have you looked for malignancies, for example MM, lymphoma,  MDS, smoldering MM, checked her bone marrow? I would anyhow.

I also see somewhat low (or very high % of) naive Bs in adults with phenotypes more like CID than CVID, many of whom even after WES lack an established diagnosis. They often have low naive CD4 and CD8 cells as well.

Not much of help I am afraid?

Mikko

Oyl Mikko Seppänen
Harvinaissairauksien yksikkö (HAKE)
[cid:]

Head, Rare Disease Center,
Helsinki University Hospital (HUH)
FINLAND

phone +358 947180201
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CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> kirjoitti 15.2.2017 kello 21.50:

Dear colleagues,

I would greatly appreciate advice regarding immune findings in 2 adult patients.

Patient 1 is a 55 year-old lady referred to me with a 4 year history of recurrent URTI’s (bronchitis, sinusitis) and pneumonia in December 2016. Blood tests revealed selective reduction in serum IgG of 5.32 g/L (7-16), normal IgM & IgA. Protective specific IgG against Diphtheria & tetanus, Haemophilus Influenza B – 2mg/L ( >1.5 ), Strep Pneumonia 46.1 mg/L ( >35 ). Unfortunately, we don’t have access to individual Strep pneumonia serotypes. Secondary causes of Protein loss and malignancy were excluded. Immune subsets revealed raised CD3+ (5101) with raised CD4 & CD8 but normal CD4/8 ratio, normal NK and B-cells absolute counts. B-cells - 9.65%, Total memory B-cells (19+27+) 35%, Naïve B-cells (19+D+M+ 27-) 62.8%, IgM memory (19+D+M+27+) 23 %. Class switched (19+27+M-D-) & Non-class switched (19+27+D+M-) are both 0%. In some ways this B-cell profile is a mirror image of the CVID patients Joe Church recently posted with normal switched memory B cells and poor vaccine responses.
The reduced serum IgG could be due to intermittent steroid use over the past 2 years. Any support for Ig replacement (may be difficult to fund because of intact vaccine responses, but absent switched memory subset may help)?
Any one favor AB prophylaxis at this stage and just monitor?

2nd patient is a 70 year-old lady admitted with bilateral pneumonia, on a background of recurrent sinusitis and basal bronchiectasis. Serum IgG was mildly depressed at 6.81 g/L  with  normal range  serum IgA, IgM & IgE. Immunophenotyping revealed  normal CD3/CD4/CD8 and NK subsets.Baseline vaccination status  showed sub-protective values of specific IgG  against tetanus toxoid and Haemophilus B influenza,  but  markedly elevated  specific IgG  against strep pneumonia of 1297 (she was given Pneumovax 23 in July 2016). B-cell phenotyping  disclosed normal circulating B cells  of 21.7%,  normal total memory population of 39%, and normal class-switched B-cells  of 14.3%,  and low naive population of B-cells at 1.16%.
What is the implication of low naïve B-cells for this patient? Does it imply a restricted antibody repertoire,  resulting in  susceptibility if exposed new infectious organisms, despite normal range switched memory B-cells?

I would greatly value comments and suggestions.

Thanks & Regards,

Stan

Stan Ress
Emeritus Associate Professor of Medicine, UCT
Specialist physician & Clinical Immunologist,
UCT Private Academic hospital, Anzio Road, Observatory,
Cape Town, 7925 South Africa
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