TGI Friday! Our weekly round-up of recently published research abstracts | 5 December 2014

From Immunologic Research, 27 November 2014 2014 [Epub ahead of print].

Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA).

Agmon-Levin N, Zafrir Y, Kivity S, Balofsky A, Amital H, Shoenfeld Y.
The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, 52621, Tel-Hashomer, Israel.


The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination.

Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations.

In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients.

The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year.

Eight (42.1 %) patients continued with the immunization programdespite experiencing adverse events.

Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complainrs (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All
patients fulfilled the ASIA criteria.

This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk factors. ASIA criteria
were fulfilled in all patients eluding the plausible link between ASIA and CFS/FM.

From The Journal of Autoimmunity, article accepted 13 October 2013. Link takes reader to full text.


Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects

Carlo Perricone (a,b), Serena Colafrancesco (a,b), Roei D. Mazor (a), Alessandra Soriano (a,c), Nancy Agmon-Levin (a), Yehuda Shoenfeld (a,d,*)
a) The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
b) Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, )Sapienza Università di Roma, Rome, Italy
c) Department of Clinical Medicine and Rheumatology, University Campus Bio-Medico of Rome, Italy
d) Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel


In 2011 a new syndrome termed ‘ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants’ was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect.

All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with postvaccination phenomena and macrophagic myofasciitis syndrome.

Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena.

This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance.

From Neuroendocrinology Letters, 2 November 2014 [Epub ahead of print].

Evidence for the existence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with and without abdominal discomfort (irritable bowel) syndrome.

Maes M(1), Leunis JC(2), Geffard M(3), Berk M(4).
1) Maes Clinics @ TRIA, Bangkok, Thailand, Thailand.
2) Laboratory Ategis, Wavre, Belgium.
3) Association Institute for Research and Development in Human Pathology and Therapy, Talence, France.
4) Department of Psychiatry, Deakin University, Geelong, Australia.



There is evidence that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is accompanied by gastro-intestinal symptoms; and IgA and IgM responses directed against lipopolysaccharides (LPS) of commensal bacteria, indicating bacterial translocation.


This study was carried out to examine gastro-intestinal symptoms in subjects with ME/CFS versus those with chronic fatigue (CF). The two groups were dissected by dichotomizing those fulfilling and not fulfilling Fukuda’s critera. In these groups, we examined the association between gastro-intestinal symptoms and the IgA and IgM responses directed against commensal bacteria.


Using cluster analysis performed on gastro-intestinal symptoms we delineated that the cluster analysis-generated diagnosis of abdominal discomfort syndrome (ADS) was significantly higher in subjects with ME/CFS (59.6%) than in those with CF (17.7%). The diagnosis of ADS was strongly associated with the diagnosis of irritable bowel syndrome (IBS). There is evidence that ME/CFS consists of two subgroups, i.e. ME/CFS with and without ADS. Factor analysis showed four factors, i.e. 1) inflammation-hyperalgesia; 2) fatigue-malaise; 3) gastro-intestinal symptoms/ADS; and 4) neurocognitive symptoms. The IgA and IgM responses to LPS of commensal bacteria were significantly higher in ME/CFS patients with ADS than in those without ADS.


The findings show that ADS is a characteristic of a subset of patients with ME/CFS and that increased bacterial translocation (leaky gut) is associated with ADS symptoms. This study has defined a pathway phenotype, i.e bacterial translocation, that is related to ME/CFS and ADS/IBS and that may drive systemic inflammatory

From Cytokine, 15 November 2014. [Epub ahead of print]

The relationship between interleukin-6 in saliva, venous and capillary plasma, at rest and in response to exercise.

Cullen T(1), Thomas AW(2), Webb R(2), Hughes MG(3).
1) Cardiff School of Sport, Cardiff Metropolitan University, Cardiff CF23 6XD, UK. Electronic address:
2) Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff CF5 2YB, UK.
3) Cardiff School of Sport, Cardiff Metropolitan University, Cardiff CF23 6XD, UK.


IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise. The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma.

Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA).

In Trial A venous plasma IL-6 increased significantly from 0.4±0.14pg/ml to 0.99±0.29pg/ml (P<0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change. In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22±0.18 to 0.74±0.28pg/ml (P⩽0.01); capillary: 0.37±0.22 to 1.08±0.30pg/ml (P<0.01). Venous and capillary plasma responses did not correlate at rest (r=0.59, P=0.07) but did correlate post exercise (r=0.79, P⩾0.001) and when expressed as an exercise induced change (r=0.71, P=0.02). Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise.


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