Autoimmune hearing loss tests - From Ray Mullins

Ray Mullins asks:

Are there useful tests available in Aust for suspected autoimmune
hearing loss?
And does anyone have useful advice for management and assessment of benefit
other than frequent hearing tests?

Ab to Zn Transporter 8 - From Len Harrison

Dear all

Thanks to Len Harrison for  informing us of an assay for measurement of antibodies to "ZnTx8 Ab is measured by IP of 35S-methionine labeled in vitro translated protein, in the Endocrine Lab at the Royal Melbourne (contact Prof. Peter Colman). " Len

Immunology forum question - Zinc transporter 8 antibody - from David Heyworth-Smith

Greetings.  Is anyone offering routine testing of zinc transporter-8 autoantibodies?  We (QML) have received a solitary request.  My brief scanning of the literature suggests measurement may have some additive predictive value to anti-GAD and anti-IA2 in relatives of type 1 diabetics and also in assessment of late onset autoimmune diabetes.  Many thanks for any information and comments.
Kind regards
David

Dr. David Heyworth-Smith
Clinical Immunologist
QML Pathology
ph 07 31214444
david.heyworthsmith@qml.com.au

Ferroxidase activity in heterozygous caeruloplasmin states - Reply from Marv Fritzler to Damun Langguth

Thanks for the offer.  We have set up a good assay on Luminex with the help of several controls from the johns Hopkins group. I do many of my assays for a group of consultants in Quebec who have become very good at making the clinical diagnosis. In our hands at least 25% of high positives have no traceable history of current or past statin use.  What is you experience?

Hope to see you in 2014 when AI travel down under for the RCPA. 

- Marv

Assay Query (Aceruloplasminemia) - From Marv Fritzler

Dear all
Any help that can be provided for this query would be greatly
appreciated. 

"Is anyone doing the ferroxidase activity test (in order to further
validate a heterozygous genetic result for aceruloplasminemia)" - Marv Fritzler

Scleroderma-Associated Antibody Testing - From Theo deMalmanche

Dear colleagues,

  Can I ask who is offering testing for SSc associated Abs?  Particularly interested in the Th/To (we do RNAPIII by ELISA, and Ku is on the muscle LIA).

  A bit embarrassing that we don't already do these, but the validation process is a little tricky (and only a few antigens aren't on other EIA/LIA).

Thanks,

Theo

The LAMP Discussion on Immunology Groups Forum

Dear All

Apologies to those who received this previously, but I wished to inform you that this lively discussion on LAMP antibodies has now been posted to website

Regards

Glenn

LAMP - From Marv Fritzler

Sometimes rhetorical questions come across as conclusions.

This paper only deals with particular entities that had been claimed by another group  to have anti-LAMP-2 who also claimed they were pathogenic and had a molecular mimic.

All I am saying is that the paper you cite should not be taken to dismiss that anti-LAMP-2 have other clinical associations or that they don't exist.

 

 

Marvin J Fritzler PhD MD

Professor of Medicine

Chair: Alberta Research & Innovation Authority (ARIA)

LAMP - From David Fulcher

Well it was actually a question not a conclusion, but the data, showing a high false-positivity rate in UTI, rather limits the diagnostic value, right? And their large cohort, and failure to reproduce (what I thought was a very impressive initial paper), casts doubt in my mind anyway.

LAMP - From Marvin Fritzler

Careful on what you conclude is debunked...have a careful look at the conclusion.

 

Marvin J Fritzler PhD MD

Professor of Medicine

Chair: Alberta Research & Innovation Authority (ARIA)

LAMP Antibodies - Response From David Fulcher

Hasn't the lamp-2 story been debunked??

LAMP Antibodies - From Marvin Fritzler

we do anti-LAMP-2 in Calgary.

 

 

Marvin J Fritzler PhD MD

Professor of Medicine

Chair: Alberta Research & Innovation Authority (ARIA)

LAMP Antibodies

Dear All,

  A request from one of our renal physicians really.  Does anyone know of available testing for antibodies to LAMP (LAMP-2, I presume)?

  (young male pt with 14/17 glom with crescents, Ab neg on DIF and IIF, incl ANCA etc.)

Thanks,

Theo

FceRI Antibodies - From William Smith

My understanding is that there are still no commercial tests, the area has been difficult for technical reasons and also for reasons of test peformance- poor specificity in immunoassays, poor correlation between immuno and functional assays. Functional assays (BAT and histamine release) remain gold standard but reproducibility is poor and difficult to commercialise.
Regards, William

Anti-FcERIa and anti-IgE

Hi Martyn,

I came across this from the Mayo Clinic: http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=91788

It looks like the test is done by National Jewish, and they look at CD203c upregulation on donor basophils.

Has anyone here sent them serum before?

I have been testing for anti-FcERIa and anti-IgE by an in-house RIA for research. However, this has not been validated yet. 

Priscilla

Priscilla Auyeung 

PhD student
Harrison Lab
Walter and Eliza Hall Institute
1G Royal Parade, Parkville, VIC 3052, Australia
Tel: +61 3 9345 2459
Fax: +61 3 9345 2911
auyeung@wehi.edu.au

Autoantibodies to FceRI or IgE

Is anyone aware of the availability of assays for autoantibodies to FceR1a or IgE?

 

Martyn

 

Professor Martyn A French MB ChB, MD, FRCPath, FRCP, FRACP
Clinical Immunologist, Department of Clinical Immunology, Royal Perth Hospital and PathWest Laboratory Medicine
Winthrop Professor in Clinical Immunology and Deputy Head, School of Pathology and Laboratory Medicine, University of Western Australia
Telephone: +61-8-92242899
Fax: +61-8-92242920
E-mail: martyn.french@health.wa.gov.au (hospital); martyn.french@uwa.edu.au (university)

GAD65 & GAD67

Dear Glenn,

 

The current literature on anti-GAD and Stiff-Person Syndrome and/or cerebellar ataxia doesn't discuss GAD67 any more. It is agreed that the antigen recognised is a different epitope on GAD65 to that recognised by diabetics without SPS (Solimena M and Carmilli PD TINS, 14(10) 452, 1991).

 

The majority of patients with SPS or cerebellar ataxia produce a "cobble-stone" immunofluorescence pattern in the granular layer on monkey cerebellum (see attached PDF). We screened around 20 diabetics with high levels of anti-GAD (RSR ELISA) with no evidence of neurological disease and none demonstrated the "cobble-stone" pattern. This suggests that the SPS sera recognize a fixation-dependent epitope on GAD65.

 

The presence of anti-amphiphysin IIF (and anti-amphiphysin blot positive) in patients with anti-GAD increases the likelihood of a tumour.

 

Regards

Bob Wilson

GAD65 & GAD67

Dear All

As you know the GAD antibody seen in Stiff-Person Syndrome is picked up on islet cell substrate (see picture below), even though this is usually used to detect the anti-GAD65 antibodies seen in DM Type I

Is anyone in our group aware of potential utility &/or availability of more specific antibody test for the GAD67 antigen which is more associated with the autoimmune condition affecting brain? Or are they so similar structurally that a cross-reactive antibody is adequate?

Any input welcomed

Regards

Glenn

Anti-GAD IIF Monkey Cerebellum:

Pancreas GAD Staining:

TLR3 & Related Pathways

Both EBV and VZV have very differing life cycles to HSV1 and 2. EBV and VZV both replicate expressing intracellular levels of viral transcripts during clinical quiescence. During quiescence HSV and 2 do  not express viral transcripts, though curiously, HSV 1 and 2 have asymptomatic viral shedding though this does not occur in EBV and VZV.

 

All (except VZV I think) have IL-10 homologues (as does CMV) thought used to prevent the harbouring site being destroyed, though on VZV this perhaps is not useful.

 

Surely his lymphopenia is key.

 

I have a man in mid 50's presented with necrotizing HSV2 (genital) and subsequently has had 3 cutaneous melanoma, and 2 KS. He isn't of the genetic background for KS, and he has neg HIV, but he does have a CD4 count that floats 200-350.

 

I think like in HIV, some people can get CD4 depletion for specific viruses (perhaps under direction of some malfunctioning CD4 memory maintenance).

TLR3 Signalling and Related Pathways

Dear Daman and Stephen,

Thanks for your replies.

 

Daman - I guess there is a reason why patients with TLR deficiency tend to present with HSV rather than other herpesviruses - I must say that you are probably better read up on this than me. But if anyone has a suggestion as to what might be common, it would be welcome. It could be pure coincidence that they are both herpesviruses rather than other opportunistic infections, but it is intriguing...

 

Stephen - He did have EBV NA IgG detected - so I guess it may be reactivation. Unfortunately they did not do any IgM serology at the time (lymphadenopathy occurred back in September) and it may be a bit late now. He had a BM biopsy yesterday and we are waiting for the result.

 

I'll let you know if anything eventuates.

 

Regards,

Catherine

TLR3 Signalling & Related Pathways: From Daman Langguth

Dear Daman and Stephen,

Thanks for your replies.

 

Daman - I guess there is a reason why patients with TLR deficiency tend to present with HSV rather than other herpesviruses - I must say that you are probably better read up on this than me. But if anyone has a suggestion as to what might be common, it would be welcome. It could be pure coincidence that they are both herpesviruses rather than other opportunistic infections, but it is intriguing...

 

Stephen - He did have EBV NA IgG detected - so I guess it may be reactivation. Unfortunately they did not do any IgM serology at the time (lymphadenopathy occurred back in September) and it may be a bit late now. He had a BM biopsy yesterday and we are waiting for the result.

 

I'll let you know if anything eventuates.

 

Regards,

Catherine

TLR3 and Related Pathways: Response from Stephen Adelstein

Catherine,

 

Does he have EBV antibodies?  I would not be dissuaded from considering XLP especially if he does not have anti-EBV antibodies – only a third of patients with XLP have immunodeficiency as far as I understand.  Age is obviously against him, but manifestation of the condition does require exposure to EBV and conceivable (albeit unlikely?) that this had not happened previously…?

 

Would however be concerned about primary marrow problem with secondary VZV and EBV.  Assume rest of haematopoetic cells are normal ? Has he had a bone marrow exam? Etc

 

SA

 

 

 

Stephen Adelstein

Head, Department of Clinical Immunology | Royal Prince Alfred Hospital
Missenden Road, Camperdown, NSW 2050 Australia
Tel 02 9515 7585 | Fax 02 9515 7762 | stephen.adelstein@sydney.edu.au

TLR Signalling: Response from Daman Langguth

Catherine,

 

VZV reactivation is entirely controlled by CMI specific to that virus and I don't think dependant on TLR at all.

 

He may have an idiopathic CD4 deficiency or CD8 for that matter (although VZV specific CD4 are the predominant cell in the sensory neural ganglia).

 

It might be interesting to see if he has ever had testing for EBV prior or if he had evidence for reactivation or acute infection of EBV. Given his age this could well be reactivation a la EBV lymphoprolif disease.

 

HHV4 (VZV)and EBV have a totally different lifestyle and immunology to HSV1 and 2 (and to HHV6 and 8 for that matter) so wouldn't lump all the herpseviruses together.

 

I don't think that helps much though.

 

Daman Langguth

Wasting too much time on immunology of varicella.

TLR3 Signalling Pathways

Dear all,

We have a 48 y.o man, previously well, who this year has had an episode of florid multidermatomal VZV, followed a few weeks later by lymphadenopathy with EBV detected in lymph nodes, then progressive ataxia with EBV in CSF by PCR. He has no family history of immunodeficiency, and no identifiable malignancy nor lymphoma.  There is no history of HSV encephalitis

His labs show polyclonal hypergammaglobulinaemia and a pan B and T lymphopaenia, total lymphocytes 0.5 x 10^9/L (? a result of the viral infection). Repeatedly HIV negative.

He seems to have acquired a problem with herpesviruses - does anyone in Australia do TLR3 sequencing? Or have an interest in investigating that pathway?

Given his generalised lymphadenopathy (not that big - only up to 12mm) with EBV in the nodes, would anyone consider XLP in a man of this age, and without hypogammaglobulinaemia?

Thanks for your thoughts,

Catherine Toong
Immunologist
Liverpool hospital, Sydney.

LAMP Antibodies

Dear All,

  A request from one of our renal physicians really.  Does anyone know of available testing for antibodies to LAMP (LAMP-2, I presume)?

  (young male pt with 14/17 glom with crescents, Ab neg on DIF and IIF, incl ANCA etc.)

Thanks,

Theo

Fwd: 23 month old with ?IFNgR Deficiency

---------- Forwarded message ----------
From: glenn reeves <glenn.reeves@gmail.com>
Date: Wed, Nov 14, 2012 at 8:28 PM
Subject: 23 month old with ?IFNgR Deficiency
To: ImmDefClin <glenn.reeves.lgidc@blogger.com>, ImmDefLab <glenn.reeves.lgidls@blogger.com>


Ben, post cam path, t-cell reconstitution may not necessarily be normal, so I would be careful implying that a total lymph count implies a normal cd4 count.

In addition, in adult non HIV non drug induced immune suppression NTMI relapses are common. This seems true in the Thai anti-ifn antibody PTs as well as the idiopathic disease largely in elderly women who haven't been shown as yet to have ifn-g pathway defects.

Dr Daman Langguth
MBChB FRACP, FRCPA
P:07 3377 8698
M:0414642282
F:07 3871 1877

23 Month Old with ?IFNgR deficiency

 Dear All,
>
> We've been consulted about a 23/12 old patient at the kids hospital in
> Perth who has developed disseminated non TB mycobacterium after Campath
> therapy for refractory Langerhan's Cell Histiocytosis (Histopath have
> assured us that the diagnosis is correct although there have been
> reports of LCH mimicing IFNgR deficiency which is known to respond to
> IFNg therapy).
>
> They've asked us about IFN g therapy as an option in this patient who
> has developed relapsed NTM involving the skin despite clarithromycin,
> rifabutin and ciprofloxacin. We are looking for a biomarker to prove IFN
> g pathway deficiency before embarking on this. Steve Holland from NIH
> has suggested doing CD119 (IFNgR1) on peripheral blood as an initial
> screen. We've found the Addenbroke's Hospital in the UK will examine the
> IL-12/IFNg/IFNgR pathway for us but we're wanting to know if anyone in
> Australia is doing this or has experience?
>
> Regards,
>
> Dr. Ben McGettigan
> Immunology Advanced Trainee
> Dept of Clinical Immunology
> Princess Margaret Hospital
> GPO Box D184 Perth WA 6840
> Ph  (08) 9340 - 8310
> Fax  (08) 9380 6246