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

Sun Feb 19 12:19:33 EST 2017

Just regarding looking for MDS or lymphoma in this patient .... If the CBC
is normal then I would not do a marrow to look for MDS.  It wouldn't change
anything that you do (i.e. you wouldn't treat the MDS at this stage).  If
you scan the patient looking for lymph nodes, then you are going to have to
biopsy if you find an enlarged node.  If the patient has a normal LDH and
does not have any B symptoms, palpable splenomegaly or lymph nodes then I
would not scan the patient.  I think you would be over-investigating and
potentially subjecting her to unnecessary procedures.

If she happened to have a lymphocytosis on CBC (in spite of the low B cell
subsets), then I would do flow cytometry looking for a clonal population of
cells.  CLL is well known to cause derangements in humeral immunity.  That
said, I've never done B cell subsets on a patient with CLL, but they
apparently can have increased naive or memory B cells.
http://www.nature.com/leu/journal/v16/n12/full/2402731a.html

Jen

Jennifer Grossman
Hematologist
Department of Hematology and Hematologic Malignancies
Alberta Health Services

On Thu, Feb 16, 2017 at 3:12 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
wrote:

> 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>
> Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net>
> Date: Thursday, 16 February 2017 at 7:25 AM
> To: CIS-PIDD <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)
>
> Head, Rare Disease Center,
> Helsinki University Hospital (HUH)
> FINLAND
>
> phone +358 947180201 <+358%209%2047180201>
> GSM +358 50 4279606 <+358%2050%204279606>
> fax +358 9 47174703 <+358%209%2047174703>
>
> CIS-PIDD <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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