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