Retrovirus in salivary glands from patients with Sjgren's syndrome

[natasa778]

http://jcp.bmj.com/content/50/3/223.abstract

CONCLUSIONS: The data suggest the presence of an unknown retrovirus similar to HIV in the salivary gland which might be involved in the pathogenesis of a subpopulation in Sjgren's syndrome.



On Sjogren's syndrome:

http://www.myalgia.com/sjogrens.htm

.... Fatigue is probably the most common complaint in patients with Sjgren's syndrome. Fatigue may have many causes, including those related directly and indirectly to the Sjgren's syndrome. Two types of fatigue should be considered. The first type is late morning or early afternoon fatigue. In this case, the patient arises with adequate energy but simply "runs out of gas." This type of fatigue suggests an inflammatory or metabolic process. Patients describe this type of fatigue as "flu-like" symptoms, and it results from an active immune system liberating specific hormones of inflammation called interleukins. To help determine whether fatigue is due to active inflammation, blood tests called "sedimentation rate" or "C-reactive protein" are ordered by your physician, since these tests are usually elevated by the same interleukins that cause fatigue.

A second type of fatigue is "morning fatigue," where the patient arises in the morning and does not feel that he/she has obtained an adequate night's sleep. This is also quite common in Sjgren's syndrome and may exist in addition to "inflammatory" fatigue....

 

[Gerwyn]

http://jcp.bmj.com/content/50/3/223.abstract

CONCLUSIONS: The data suggest the presence of an unknown retrovirus similar to HIV in the salivary gland which might be involved in the pathogenesis of a subpopulation in Sjgren's syndrome.



On Sjogren's syndrome:

http://www.myalgia.com/sjogrens.htm

.... Fatigue is probably the most common complaint in patients with Sjgren's syndrome. Fatigue may have many causes, including those related directly and indirectly to the Sjgren's syndrome. Two types of fatigue should be considered. The first type is late morning or early afternoon fatigue. In this case, the patient arises with adequate energy but simply "runs out of gas." This type of fatigue suggests an inflammatory or metabolic process. Patients describe this type of fatigue as "flu-like" symptoms, and it results from an active immune system liberating specific hormones of inflammation called interleukins. To help determine whether fatigue is due to active inflammation, blood tests called "sedimentation rate" or "C-reactive protein" are ordered by your physician, since these tests are usually elevated by the same interleukins that cause fatigue.

A second type of fatigue is "morning fatigue," where the patient arises in the morning and does not feel that he/she has obtained an adequate night's sleep. This is also quite common in Sjgren's syndrome and may exist in addition to "inflammatory" fatigue....

my ESR up for years

 

[usedtobeperkytina]

You know, I remember in Osler's Web that many of the Incline CFS patients had problems with salivary glands.

And this came out in 1999: http://www.prohealth.com/library/showarticle.cfm?id=352&t=CFIDS_FM

Tina

 

[Hope123]

Well, in autoimmune illnesses, there have been frequent detection of antibodies to retroviral antigens (including HIV) in people who did not have HIV by other tests or risk factors. Here, there is other data but I would suggest people read Kurt's "Human Rumor Viruses" article as that talks about the search for retroviruses in chronic illnesses. It's under the thread title "HERVs and XMRV." The description of fatigue is interesting though..........sounds like the fatigue I have.

Tina, the link goes to an article about adrenal glands, which sit on top of the kidneys, rather than salivary glands.

Gerwyn, my ESR has also been up and rising slightly. (but other rheum tests do not suggest rheum disease) This makes me wonder sometimes if people with our illness are excluded from trials because researchers have erroneosly interpreted that ALL usual tests have to be normal for research studies. In fact, the original Fukuda criteria would not exclude us as it sounds like they allow abnormalites in labs if these do not account for the fatigue.

Finally, here's an intriguing article:

Clin Infect Dis. 1994 Jan;18 Suppl 1:S28-31.
Chronic fatigue syndrome and a disorder resembling Sjgren's syndrome: preliminary report.
Calabrese LH, Davis ME, Wilke WS.
Department of Rheumatic and Immunologic Disease, Cleveland Clinic Foundation, Ohio 44195-5028.
Chronic fatigue syndrome (CFS), as currently described in the working criteria proposed by the Centers for Disease Control and Prevention (Atlanta), may be associated with multiple, distinct, and possibly unique clinical and/or etiopathogenic subsets. Sjgren's syndrome (SS) is a disease of unknown etiology that is characterized by dryness of the mucous membranes and a variety of autoimmune phenomena and conditions. Subjective manifestations of SS such as neurocognitive dysfunction and fatigue have been stressed by some observers. We have detected a large number of patients with unrecognized SS-like illness in a clinical specializing in CFS and believe the relationship to be more than casual. From January 1991 through April 1992, 172 patients were evaluated for CFS; the SS cohort consisted of 27 females (mean age, 41.9 years). Sixteen of these patients had previously been found to have CFS by a physician, and 11 were self-referred. All patients complained of severe, dominating, chronic fatigue. Complaints of myalgia were prominent; 20 of 27 patients met the criteria for fibromyalgia. Neurocognitive complaints and/or a history of neuropsychiatric disease was frequent. Results of Schirmer's test were abnormal for 16 of 27, and results of minor salivary-gland biopsy were abnormal for 20 of 25. Antibodies to nuclear antigen were present in 16 of 27, but anti-Ro was present in only 1 of 21. In the SS group, 13 of 27 patients met eight or more CDC minor criteria for CFS, and 18 of 27 met six or more of the criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

 

[natasa778]

Well, in autoimmune illnesses, there have been frequent detection of antibodies to retroviral antigens

yes to that but they also looked at: "... Mn2+ dependent, Mg2+ independent RT activity was detected in the salivary gland tissues in three of 10 patients. A-type-like retroviral particles were observed in epithelial cells of salivary glands by transmission electron microscopy ..."


Even if we allow that a-type-like retroviral particles can be due to other things, the above begs the Question: apart from an actual retrovirus is there an alternative explanation to the presence of reverse transcriptase activity?

 

[natasa778]

Here is a bit more background on the RT essays the used in the above study:
...thus, the detection of RT activity can generally indicate the presence of a retrovirus in the absence of specific information regarding its genome or protein content. Although RT assays generally detect about 105 to 106 virus particles and are not as sensitive as infectivity or PCR assays, they are broadly reactive and have been used for the detection and isolation of different types of novel retroviruses including HIV-1 (2, 6). In addition, RT assays are routinely used in infectivity studies for the rapid and easy monitoring of retrovirus infection and replication.... http://www.ncbi.nlm.nih.gov/pmc/articles/PMC84929/


So I'll repeat the question, Gerwyn, Kurt anyone please: apart from an actual retrovirus is there an alternative explanation to the presence of reverse transcriptase activity?

 

[andreamarie]

Has anyone on this board been dx with Sjogren's and CFS. I was dx with Sjogren's thirty five yrs ago but it was not a confirmed (by labs,etc) dx.I didn't have sleep disorder, PEM, or disabling fatigue until fifteen yrs ago.

 

[jessjb79]

my ESR up for years

I hope this isn't too off topic - I'm curious about the sed rate thing because I've read that some doctors, Dr. Cheney included I think, report really low sed rates in CFS patients. Several places I've read that CFS is like one of three diseases/disorders where ESR is extremely low; the other two being sickle cell and cardio myopathy I think. Mine has been tested 3 times. Results were 0,1, and 0 again. Doctors have said 'that's odd' but have never said much else about it. I'd be curious how many people have high vs low. I would think high would make most sense....

 

[Kati]

Interestingly as a child ( 30 years ago or so) I got 2 salivary glands removed due to stones- Got sick with EBV 16 months ago now-

 

[Anika]

Reverse Transcriptase - also in ALS; can HERVs be linked?

Here is a bit more background on the RT essays the used in the above study:
...thus, the detection of RT activity can generally indicate the presence of a retrovirus in the absence of specific information regarding its genome or protein content. Although RT assays generally detect about 105 to 106 virus particles and are not as sensitive as infectivity or PCR assays, they are broadly reactive and have been used for the detection and isolation of different types of novel retroviruses including HIV-1 (2, 6). In addition, RT assays are routinely used in infectivity studies for the rapid and easy monitoring of retrovirus infection and replication.... http://www.ncbi.nlm.nih.gov/pmc/articles/PMC84929/


So I'll repeat the question, Gerwyn, Kurt anyone please: apart from an actual retrovirus is there an alternative explanation to the presence of reverse transcriptase activity?

Very interesting post, and question, natasa. I hope someone knowledgeable will jump in.

There have also apparently been studies finding high rates of reverse transcriptase in ALS patients. Soon after XMRV was discovered, they tested for XMRV in one study of ALS patients, and came up empty - though it would be interesting to have those tests redone, in view of what has been learned about XMRV testing thus far.

I've seen several interesting posts talking about HERVs, human endogenous retroviruses that are part of our genome, that somehow get activated or turned on in some way - perhaps that is not the proper term. I've been a bit confused about what that means. It also leads me to wonder whether reverse transcriptase has ever been linked to HERVs in some way.

And, of course natasa your original question, is anything other than a retrovirus, exogenous or endogenous, known to explain reverse transcriptase in some cases.

 

[Hope123]

If you read the section on reverse transcriptse assay in the article I mentioned earlier, it talks about why these assays aren't foolproof. In fact, Kurt's articles mentions Sjogrens and the studies that have been done on it. The whole picture needs to be taken into account.

Re: ESR. I've heard it said too about it being low but have found no published/ labdata about this and I am reluctant to rely on just Cheney's statements. If anyone knows, please refer me to it. In my mind, an elevated ESR makes sense since that refers to non-specific chronic inflammation as well as C-reactive protein. However, surprisingly (or maybe not), there's little research on either marker in CFS. I haven't been able to read enough yetabout the correlations between cytokines and ESR. The majority of the time, low ESRs aren't as big a concern as high. Note also that elevated ESR needs to be adjusted for anemia if you have it and older age.

 

[natasa778]

Soon after XMRV was discovered, they tested for XMRV in one study of ALS patients, and came up empty - though it would be interesting to have those tests redone, in view of what has been learned about XMRV testing thus far.

I agree, they would need to be looking directly at motor neurons themselves.

 

[natasa778]

If you read the section on reverse transcriptse assay in the article I mentioned earlier, it talks about why these assays aren't foolproof. In fact, Kurt's articles mentions Sjogrens and the studies that have been done on it. The whole picture needs to be taken into account.

Yes I can see that now on RT, thanks. They don't go into any details on Sjogren's findings.
What is they repeat throughout is that one of the main reasons to establish involvement of retroviruses in any human diseases is the deeply ingrained scepticism of virologists towards new discoveries in this field.

If it was down to virologists/scientists alone, the role of HIV in human disease would not have been established. There would have been few negative studies, few review papers and editorials saying that finding something by ALL existing methods does not prove anything... the funding would have dried up and the whole thing would have died then and there.

 

[Anika]

If you read the section on reverse transcriptse assay in the article I mentioned earlier, it talks about why these assays aren't foolproof. In fact, Kurt's articles mentions Sjogrens and the studies that have been done on it. The whole picture needs to be taken into account.

Re: ESR. I've heard it said too about it being low but have found no published/ labdata about this and I am reluctant to rely on just Cheney's statements. If anyone knows, please refer me to it. In my mind, an elevated ESR makes sense since that refers to non-specific chronic inflammation as well as C-reactive protein. However, surprisingly (or maybe not), there's little research on either marker in CFS. I haven't been able to read enough yetabout the correlations between cytokines and ESR. The majority of the time, low ESRs aren't as big a concern as high. Note also that elevated ESR needs to be adjusted for anemia if you have it and older age.

Hope, thanks for your comments. On Reverse transcriptase, I'm not sure which article you're referring to - I couldn't find more than abstract on Calabrese's 1994 article you mentioned.

Re: ESR - no lab studies that I know of show that it's generally low in CFS, but I've heard it elsewhere (see below) - although it may go back to Cheney's observation. I don't think there would be any official reports, because at least when I first had the test done, there was no lower abnormal range, only a high abnormal. So reports of low sed rates are more likely to be from anecdotal clinical observations, since it's not viewed as medically significant. (One of those odd quirks, like low body temperature- though some doctors now view that as interesting from thyroid perspective.)

In my case - A specialist (not rheum) had run an ANA and ESR / sedimentation rate, and was only concerned about my slight ANA elevations. When my primary doctor saw the results, he wasn't particularly concerned with the ANA, though he ran them again later. He did make the comment that I had one of the lowest sed rates he'd ever seen, and seemed to be happy about it. (Which makes sense, if high seds reflect inflammation.) This was early when I had symptoms and was definitely not well (though fine according to the primary doctor). I think my sed rate went up slightly a few years later, after I'd been diagnosed, but still fairly low.

I think the first place I saw a reference to low sed rates was in the book Chronic Fatigue Syndrome: A Treatment Guide, by Verrillo and Gellman - which I found not long after being diagnosed. It's a 1997 book, so rather old, and they don't cite all their sources, though I saw Bell and Cheney mentioned as I tried to find the sed rate reference. They mention that often the sed rate is low, under 5, but sometimes is briefly elevated, over 20.

 

[mjay]

I hope this isn't too off topic - I'm curious about the sed rate thing because I've read that some doctors, Dr. Cheney included I think, report really low sed rates in CFS patients. Several places I've read that CFS is like one of three diseases/disorders where ESR is extremely low; the other two being sickle cell and cardio myopathy I think. Mine has been tested 3 times. Results were 0,1, and 0 again. Doctors have said 'that's odd' but have never said much else about it. I'd be curious how many people have high vs low. I would think high would make most sense....

I'm also interested in low ESR, mine has been a "1" on 4 tests since 2003 and a "2" when last tested in 2009.
I've also read that low ESR is characteristic of CFS but have not read any rationale for this, does anyone know? Doctor's haven't even commented on this result to me although my understanding is that very low does indicate something may be wrong as you suggest.
My CRP has been less than 4 which is OK.
Other posts have commented on wake up tired vs tiring out, I'm definitely in the wake up tired category. Without wake-up meds I'm lying on the couch til mid-afternoon.
Anyone else notice a relationship between ESR, +/-CRP and when fatigue is worst?

 

[natasa778]

A novel exogenous retrovirus sequence identified in humans

another one on retrovirus in Sjogren's:

A 932-bp retrovirus sequence was cloned by reverse transcriptase PCR from salivary gland tissue of a patient with Sjogren's syndrome. The sequence is related to that of type B and type D retroviruses and was present in a sucrose density gradient fraction corresponding to that of an enveloped retrovirus particle. Sequences amplified from tissues of eight individuals with or without Sjogren's syndrome had over 90% similarity and were present at a level of less than one copy per 10(3) cells. The sequence was not detectable in human genomic DNA by PCR or by Southern hybridization. These data indicate that the sequence represents an infectiously acquired genome, provisionally called human retrovirus.
DJ Griffiths, PJ Venables, RA Weiss and MT Boyd Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom. 5. J. Virol., 04 1997, 2866-2872, Vol 71, No. 4

full paper available jvi.asm.org/cgi/reprint/71/4/2866.pdf

 

[natasa778]

then later on again on HRV-5 from the same people:
Novel endogenous retrovirus in rabbits previously reported as human retrovirus 5 (2002)

Human retrovirus 5 (HRV-5) represented a fragment of a novel retrovirus sequence identified in human RNA and DNA preparations. In this study, the genome of HRV-5 was cloned and sequenced and integration sites were analyzed. Using PCR and Southern hybridization, we showed that HRV-5 is not integrated into human DNA. A survey of other species revealed that HRV-5 is present in the genomic DNA of the European rabbit (Oryctolagus cuniculus) and belongs to an endogenous retrovirus family found in rabbits. The presence of rabbit sequences flanking HRV-5 proviruses in human DNA extracts suggested that rabbit DNA was present in our human extracts, and this was confirmed by PCR analysis that revealed the presence of rabbit mitochondrial DNA sequences in four of five human DNA preparations tested. The origin of the rabbit DNA and HRV-5 in human DNA preparations remains unclear, but laboratory contamination cannot explain the preferential detection of HRV-5 in inflammatory diseases and lymphomas reported previously. This is the first description of a retrovirus genome in rabbits, and sequence analysis shows that it is related to but distinct from A-type retroelements of mice and other rodents. The species distribution of HRV-5 is restricted to rabbits; other species, including other members of the order Lagomorpha, do not contain this sequence. Analysis of HRV-5 expression by Northern hybridization and reverse transcriptase PCR indicates that the virus is transcribed at a low level in many rabbit tissues. In light of these findings we propose that the sequence previously designated HRV-5 should now be denoted RERV-H (for rabbit endogenous retrovirus H).
* Griffiths, D.J., * Voisset, C., * Venables, P.J.W. * Weiss, R.A. http://eprints.ucl.ac.uk/7168/

Does this sound like deFreitas virus?

 

[andreamarie]

about twenty yrs ago there was some noise about retrovirus in Sjogren's but it never materialized. Some Sjogren's patients have an abnormal ANA. I don't have any of the markers (only 50% do). My esr and crp are done all the time and are normal. On occasion I have an elevated white count. I was dx with Sjogren's thirty yrs ago; there was practically no interest then. Shortly after Sjogren's symptoms I got i.c. Fifteen yrs ago I got CFS. Difference is that I had flares Sjogren's when I was so fatigued I was sleeping all the time. Then I got better. No PEM or sleep disorder. Sometimes I wake up tired; usually after a crash. If I don't wake up tired and go beyond limits (can't figure them out) I'm tired later in day. I take gabapentin around 9p.m. and feel better even though I'm tired. Take second dose at bedtime with sleep med du jour.

 

[Warbler512]

Re: Sed Rate

Osler's Web (pp.214-215) references an Aussie paper, Mukherjee, et.al., Abnormal Red Blood-Cell Morphology in ME, Lancet, Aug 8 1987. The paper noted the RBCs had a "globular" or "sickled" appearance that fluctuated according to symptoms.

In a 1988 conference, Komaroff and Buchwald confirmed ESR to be rock-bottom low, i.e., 0 to 2, in about 40% of "CFS" patients, something Buchwald said was only seen in sickle cell diseases. Byron Hyde further confirmed this is only otherwise found in sickle-cell anemia, inherited sperocytosis, hyper-gammoglobulinemia and hyper-fibrogenemia. (Wikipedia, FWIW, suggests likewise.)

My initial Dx of CFS/CFIDS was made by someone familiar with Cheney's work, partly on the basis of low ESR. In nearly twelve years, I've only once seen it above 3.

By the 40% measure, ESR would not be a lone biomarker, yet I still wonder why (unless I missed something) low ESR is not mentioned in the Canadian Consensus definition. That's also led me to ask whether Byron Hyde was not picked for the author board by Health Canada or chose not to participate.

 

[natasa778]

The origin of the rabbit DNA and HRV-5 in human DNA preparations remains unclear, but laboratory contamination cannot explain the preferential detection of HRV-5 in inflammatory diseases and lymphomas reported previously.

Apart from Japanese single rubella vaccine, does anyone know of any other vaccines that are grown in rabbit cell lines? I've come across a rabies one being developed in the 80s but dont know if that one has made it through to production... Any other ones?