[CIS PIDD] some help from Chile

[Ochs, Hans]

The issue of antibody responses following Rituximab is complex but predictable: B cells are affected, plasma cells are not. So, if antibody titers to "recall antigens", e.g. tetanus, Diphtheria, are measured following Rituximab, the titers remain stable and protective; if immunized (boosted) one year after rituximab, there is often a normal response.
If a neoantigen is used, e.g. Hepatitis A vaccine, one year after Rituximab treatment was completed, there is a definite increase in titer, but less than controls not receiving R.
Using bacteriophage (a neoantigen to which there are no neutralizing antibodies in IVIG) two weeks after the last dose of Rituximab (phage is given twice, 6 weeks apart) the response is severely depressed without amplification or isotype switching post secondary. When re-immunized one year later (tertiary and quaternary immunizations), most patients showed a normal "primary and secondary" response, including amplification and isotype switching (Pescovitz Mark D, et al, JAKI 2011; 128:1295)
A neoantigen, such as bacteriophage phi X 174. or the new anti-rabies vaccine used in Holland, allows that patients can be treated immediately with IVIG and immunized independently.
hans

Hans D. Ochs, MD, Dr. med
Professor of Pediatrics | Jeffrey Modell Chair of Pediatric Immunology Research
Center for Immunity and Immunotherapies
Seattle Children's Research Institute | University of Washington

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From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of patricia roessler vergara
Sent: Saturday, July 07, 2012 5:28 AM
To: pagid at list.clinimmsoc.org; Alejandra King
Subject: Re: [CIS PIDD] some help from Chile

Thanks Jason
By now, my patient has low IgG, low IgG2 and undetectable titers anti pneumococcus (pre-vaccination).
Did you vaccinate your patient with pneumo vaccine and measure the response? or you started IGIV previously. I have that doubt because I will receive post vaccine titles in two weeks more. If they are low, I should give her a conjugate one, but in my country this means waiting 2 months for the results (thinking of waiting 6 weeks to measure again her antibodies). meanwhile I could´t give her IGIV because it can alter the interpretation of the results. From Mars she don´t have a sepsis, but before she had 10 in 18 months, so I´m afraid that waiting all this results finally she will have another sepsis
Do you think that is imprescindible to study the response to conjugate vaccines? I am practically sure that she has an alteration in polysaccharide response that will benefit with IGIV replacement. This probably will reduce her sinusitis, but what about her urosepsis?

thanks
Patricia
Patricia

2012/7/5 Jason W. Caldwell <jcaldwel at wakehealth.edu<mailto:jcaldwel at wakehealth.edu>>
This is a very intriguing case to me.  I have a very similar patient.  She was diagnosed with MS, has had recurrent sepsis (most recent Enterobacter), and has autoimmune thyroid disease.  She came to me for recurrent sinus infection and a pneumonia with respiratory failure.  She too was on rituximab in the past and has had several cycles.  My patient also has had low IgG, but her IgA is low as well.  When I checked her tetanus and dip titers where normal, but she had no response to Pneumovax.  The other intriguing similarity is that she had <1% memory B cells.

Anyway, with this picture I did start Ig replacement and she has had a reduction in sinopulmonary infections.  She did have the recent Enterobacter sepsis that is unexplained, but really is over all better.  It will be hard to say for sure if the rituximab is the cause or she started with underlying CVID.  I also have several patients that have been on rituximab for a various reasons (Burkit's lymphoma, RA, Churg-Straus, lupus) that seem to not recover B cell numbers and/or function.  I treat these patients with Ig replacement.

I would vote for giving replacement Ig.
I will be interested to see what other say about your case and question.  I would also be interested in any comment about long term B cell dysfunction after rituximab.

Jason Caldwell
Wake Forest University.

________________________________
From: pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org> [pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org>] on behalf of patricia roessler vergara [patriciaroessler at gmail.com<mailto:patriciaroessler at gmail.com>]
Sent: Wednesday, July 04, 2012 9:24 AM
To: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Subject: [CIS PIDD] some help from Chile


Dear all:
I would appreciate some help about this case:
The patient is a woman 32 years old
She carries the diagnosis of multiple sclerosis (MS), onset at the age of 15. She was treated with avonex, IV methylprednisolone and IGIV. The first years of treatment she did well but finally she continued with flare ups, so she recevied Rituxan in 2007 with good response. She recevied another round of Rituxan in 2009.
Since rituxan she did not have flares of MS until december 2011 (the one that was treated with methylprednisolone) and she did not receive another treatments
She also has a history of other autoimmune diseases: Hashimoto´s tiroiditis at age 15, seronegative Sjögren disease, positive Scl-70 and ulcerative colitis.
Her mother has a history of antiphospholipid syndrome, psoriatic arthritis and Hashimoto´s tiroiditis
She has a neurogenic bladder which has resulted in recurrent urinary tract infections. In the last 18 months she has had 10 sepsis, some of urinary origin and other from an intestinal perforation secondary to Clostridium difficile enterocolitis.
She also has 3 sinusitis per year since the last 3 years.
I saw her last week for the first time and this are the immunologic labs until now:
Oct 2011: IgG  445 (nr: 639-1349), with normal IgM and IgA
May 2012: IgG 633, with normal IgM and IgA
I order other labs:
-       specific anti pneumococcal antibodies: pending
-       CD3, CD4, CD8, CD19 and CD56 all within normal range in number and percentage
-       Naive B lymphocytes CD19+IgD+CD27- :     82 (nr: 39-84)
-       Memory B lymphocytes without isotypic switch CD19+IgD+CD27+ : 1 (3-20)
-       Memory B lymphocytes with isotypic switch CD19+IgD-CD27+:  3 (6-35)

Abdomen scan: innumerable subcentimeter pulmonary nodules at the lung bases. Torax scan: pending

Questions:
-       Can this immunologic findings, specifically those concerning CD27, be secondary to Rituxan? Or we are talking about a common variable immunodeficiency that has result in all of her autoinmune diseases (I incline for this )
-       They are planning to give her Rituxan again because she is recurring in her neurologic symptoms. What do you think about that?
- Would you give her IGIV even though we still haven´t got the specific anti pneumococcal antibodies

Thanks,

Patricia Roessler
Immunologist
Chile



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