Falaschi, P.

Martocchia, A.

English

PubMed

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65
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with concomitant fracture; although some authors recommend
one attempt at closed reduction, it is likely that such patients
will require open reduction with fixation of the fracture, so
early consultation with an orthopaedic surgeon is advisable [7,
8]. If closed reduction appears successful, the arm should be
immobilised and post-reduction radiographs should be
obtained to verify placement and identify any new fractures.
Patients with posterior shoulder dislocations should be
seen by an orthopaedic surgeon, either in the ED or within
5–7 days after discharge, and the patient should remain in a
shoulder immobiliser until this evaluation. Some patients
may require early surgical intervention, while others may be
treated with immobilisation [9]. Rotator cuff exercises or
physical therapy can be useful in preventing recurrence of
dislocation, especially in those with seizure disorders who
are at risk of future dislocations during seizures [10].
We report a case of bilateral posterior shoulder disloca-
tions that were identified and successfully reduced in the ED.
Posterior shoulder dislocations occur rarely but are often
missed on initial presentation, resulting in ongoing patient
discomfort, long-term morbidity and elevated health care
costs. Posterior shoulder dislocations should be considered
in post-ictal patients with shoulder pain or an abnormally
appearing shoulder. ED physicians may attempt to reduce the
dislocation if there is no concomitant fracture, but early con-
sultation with orthopaedic surgery is often advisable.
References
1. Ufberg J, McNamara R (2003) Management of common dis-
locations. In: Roberts JR, Hedges JR (eds) Clinical procedures
in emergency medicine, 4th edn. W.B. Saunders Company, St.
Louis, pp 948–960
2. Price DD, Wilson SR (2006) Dislocations, shoulder. Available
at: http://www.emedicine.com/emerg/topic148.htm. Accessed
14 April 2006
3. Moukoko D, Ezaki M, Wilkes D, Carter P (2004) Posterior
shoulder dislocation in infants with neonatal brachial plexus
palsy. J Bone Joint Surg Am 86:787–793
4. Elberger ST, Brody G (1995) Bilateral posterior shoulder dis-
locations. Am J Emerg Med 13:331–332
5. Hawkins RJ, Neer CS 2nd, Pianta RM, Mendoza FX (1987)
Locked posterior dislocation of the shoulder. J Bone Joint
Surg Am 69:9–18
6. Shaw JL (1971) Bilateral posterior fracture-dislocation of the
shoulder and other trauma caused by convulsive seizures. J
Bone Joint Surg Am 53:1437–1440
7. Ogawa K, Yoshida A, Inokuchi W (1999) Posterior shoulder
dislocation associated with fracture of the humeral anatomic
neck: Treatment guidelines and long-term outcome. J Trauma
46:318–323
8. Tellisi NK, Abusitta GR, Fernandes RJ (2004) Bilateral poste-
rior fracture dislocation of the shoulders following seizure.
Saudi Med J 25:1727–1729
9. Quillen DM, Wuchner M, Hatch RL (2004) Acute shoulder
injuries. Am Fam Physician 70:1947–1954
10. Sankar B, Aby NG, Rameto AS et al (2004) Spontaneous
reduction of posterior shoulder dislocation following repeated
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Intern Emerg Med (2007) 2:65–67
DOI 10.1007/s11739-007-0018-x
Amino acid sequence homologies
between HCV polyprotein and
thyroid antigens
A. Martocchia • P. Falaschi
A. Martocchia • P. Falaschi
Department of Medicine
II Faculty of Medicine
University of Rome “La Sapienza”
Rome, Italy
A. Martocchia ()
c/o Prof. Paolo Falaschi
S. Andrea Hospital
Via di Grottarossa 1035, I-00189 Rome, Italy
e-mail: a_martocchia@virgilio.it
Received: 25 May 2006 / Accepted in revised form: 31 August
2006 / Published online: 31 March 2007
Recent evidence in the literature suggests that molecular
mimicry between viral and self antigens may be involved in
the pathogenesis of autoimmune thyroid diseases in patients
with chronic hepatitis C virus (HCV) infections [1–3].
Chronic HCV infection has been reported to be associated
with thyroid autoimmunity and thyroid function disorders
with a mean incidence of 10% and 3%, respectively [4, 5].
Alfa-IFN therapy may exacerbate or induce underlying latent
thyroid disorders, increasing the incidence of thyroid
autoimmunity and thyroid function disorders to 20% and
11%, respectively [4, 5].
In keeping with the tenets of the clonal selection theory
of acquired immunity, an infectious agent may circumvent
the deletion of anti-self lymphocytes activating clones with
receptors sufficiently degenerated to respond to mimicking
epitopes and host antigens [6].
A minimum of five to six amino acids are necessary to
induce an immune response, and the probability of 20 amino
acids occurring in six identical residues between two pro-
teins is 206 (for each peptide, irrespective of the sequence) or
1 in 128 000 000 [7].
We performed the comparison between the amino acid
sequence of the HCV polyprotein and five tissue-specific
antigens of human thyroid, available in the database on
www.ncbi.nlm.nih.gov/pubmed.
In particular, we examined the following HCV genotypes
(with the respective NCBI sequence identification number):
HCV1a (GI:130455), HCV1b (GI:130469), HCV1c
(GI:385131), HCV2a (GI:130466), HCV2b (GI:130468),
66
HCV2c (GI:555104), HCV3a (GI:514395), HCV3b
(GI:676877), HCV4a (GI:402474), HCV5a (GI:2462303)
and HCV6a (GI:2326455).
Regarding the thyroid gland, we examined the following
tissue-specific antigens: the thyroglobulin (Tg)
(GI:12644093), the thyroid peroxidase (TPO) (GI:129830),
the thyrotropin receptor (TSHr) (GI:136448), the
sodium/iodide symporter (NaIS) (GI:12643359) and
Pendrin (GI:6174895).
Sequence alignments were carried out using the
BLASTp, short nearly exact matches and BLASTp2 pro-
tein–protein comparison program (available at
www.ncbi.nlm.nih.gov/BLAST).
Amino acid sequence homologies between the HCV
polyprotein and the thyroid antigens are given in detail in Fig.
1, showing the presence of identical/conservative residues in
the peptides. The following proteins of the HCV polyprotein
have been examined: C (capsule, core protein), E1 (envelope
glycoprotein 1), E2 (envelope glycoprotein 2, NS1), p7, NS2
(non-structural protein 2), NS3 (non-structural protein 3, pro-
tease/helicase), NS4a (non-structural protein 4a), NS4b (non-
structural protein 4b), NS5a (non-structural protein 5a) and
NS5b (non-structural protein 5b, RNA polymerase).
The homologies between the thyroid and the viral pep-
tides ranged from 62.5 % (five identical residues out of eight
amino acids in the sequence) to 87.5% (seven identical
residues out of eight amino acids in the sequence). The fre-
quency of the homology increased up to 100%, when the
conservative substitutions were included in the analysis (ten
out of ten identical/conservative amino acids in the sequence,
as indicated in Fig. 1 for NaIS444 and HCV1a-NS4a1665).
We found the presence of short peptides (eight to eleven
amino acids) with a high degree of homology (62.5–100%)
between the HCV polyprotein and five thyroid antigens (Tg,
TPO, TSHr, NaIS and Pendrin).
The homology was not restricted to a single HCV geno-
type or to a single thyroid antigen.
The highest degree of homology was between the NaIs
and the HCV1a-NS4a protein. The Tg antigen had the high-
est number of homologies with the different HCV genotypes.
Previous studies examining 20 amino acid-length pep-
tides showed 41.7–58.3% sequence homologies between
TPO and HCV-NS5a and HCV-NS2, increased to 75.0%
when including conservative/identical residues [3].
We found mimicry between the TSH-r and the N-termi-
nal hypervariable region 1 (HVR1) of E2 in HCV1a, which
is well known to be involved in chronic HCV infection [8].
The length of the short peptides is consistent with the
presentation of the self/viral antigens with the I class
HLA molecules to CD8 positive lymphocytes, as the II
class HLA molecules usually bind longer peptides, and
the mimic peptides may be involved in the acceleration of
autoimmune disorders occurring in chronic HCV infec-
tion [9]. In our examination, the RLGVRATRK-HCV2b-
C43 sequence presented homology with the RLGVN-
VTWK-Tg1361 sequence; the same viral peptide has been
recently identified as a HLA-A3 supertype-restricted
cytotoxic T-lymphocyte epitope in patients with HCV
infections [10].
The more frequent and earlier appearance of anti-Tg anti-
bodies in the clinical course of the thyroid autoimmunity in
HCV IFN-treated patients may be related to the high number
of homologies between the Tg antigen and the HCV polypro-
tein, whereas the anti-TPO antibodies reflect a more advanced
and aggressive autoimmune thyroid destruction [11].
Further studies are necessary in order to evaluate the clin-
ical relevance of the presence of the molecular mimicry
between the HCV and the thyroid antigens in the progression
of autoimmune disease.
References
1. Czaja A et al (1995) Immunologic features and HLA associa-
tions in chronic viral hepatitis. Gastroenterology 108:157–164
2. Muratori L, Bogdanos DP, Muratori P et al (2005)
Susceptibility to thyroid disorders in hepatitis C. Clin
Gastroenterol Hepatol 3:595–603
3. Oppenheim Y, Ban Y, Tomer Y (2004) Interferon induced
autoimmune thyroid disease (AITD): a model of human
autoimmunity. Autoimmun Rev 3:388–393
4. Prummel MF, Laurberg P (2003) Interferon-alpha and autoim-
mune thyroid disease. Thyroid 13:547–551
5. Hsieh MC et al (2000) Virologic factors related to interferon-
Fig. 1 Amino acid sequence homologies between the thyroid anti-
gens and the HCV polyprotein (see text for abbreviations). *,
Identical residues; +, conservative substitution. In each sequence,
the first left-side residue inside the box corresponds to the num-
ber of the amino acid sequence. Amino acids in standard single
letter code
67
C E
alpha-induced thyroid dysfunction in patients with chronic
hepatitis C. Eur J Endocrinol 142:431–437
6. Cohen IR (2001) Antigenic mimicry, clonal selection and
autoimmunity. J Autoimmun 16:337–340
7. Oldstone MBA (1998) Molecular mimicry and immune-medi-
ated diseases. FASEB J 12:1255–1265
8. Weiner AJ, Geysen HM, Christopherson C et al (1992)
Evidence for immune selection of hepatitis C virus (HCV)
putative envelope glycoprotein variants: potential role in chron-
ic HCV infections. Proc Natl Acad Sci USA 89:3468–3472
9. Christen U, Edelamn KH, McGavern DB et al (2004) A viral
epitope that mimics a self antigen can accelerate but not initiate
autoimmune diabetes. J Clin Invest 114:1290–1298
10. Chang KM, Gruener NH, Southwood S et al (1999)
Identification of HLA-A3 and –B7-restricted CTL response to
hepatitis C virus in patients with acute and chronic hepatitis C.
J Immunol 162:1156–1164
11. Carella C, Mazziotti G, Amato G, Breverman LE, Roti E (2004)
Interferon-? related thyroid disease: pathophysiological, epi-
demiological and clinical aspects. J Clin Endocrinol Metab
89:3656–3661
Intern Emerg Med (2007) 2:67–70
Transient massive hyperlipidaemia
in a type 2 diabetic subject
G.B. Vigna • A. Passaro • K. Bonomo • G. Anfossi
R. Fellin • M. Trovati
G.B. Vigna () • A. Passaro • R. Fellin
Section of Internal Medicine, Gerontology and Geriatry
Department of Clinical and Experimental Medicine
University of Ferrara
Via Savonarola 9, I-44100 Ferrara, Italy
e-mail: vgg@unife.it
K. Bonomo • G. Anfossi • M. Trovati
Diabetes Unit
Department of Clinical and Biological Sciences
University of Turin
San Luigi Gonzaga Hospital, Orbassano (Turin), Italy
Received: 7 April 2006 / Accepted in revised form: 13 September
2006 / Published online: 31 March 2007
A 50-year-old man, in apparently good health, was referred
to the Lipid Center of San Luigi Gonzaga Hospital,
Orbassano (Turin, Italy), by his primary care physician
(PCP) because clinical tests at the time of blood donation
showed milky plasma with serious hypertriglyceridaemia
(>5000 mg/dl) and hyperglycaemia (381 mg/dl), diagnostic
for diabetes. It was not possible to perform further blood
chemical analyses because hypertriglyceridaemia would
have provided abnormal results. The patient entered the hos-
pital to prevent acute pancreatitis, which is often associated
with severe hypertriglyceridaemia.
The clinical history revealed H. pylori-associated gas-
tric ulcer in the prior year. At that time, laboratory tests dis-
closed “mild” hyperglycaemia and hypertriglyceridaemia
(the patient’s records were misplaced.) An ill-defined
hypolipidaemic diet was recommended at discharge, but the
suggestion was neglected. He was a former smoker (30
pack year, stopping about 10 years before), and consumed
a diet rich in saturated fats and carbohydrates while alcohol
ingestion was mild and occasional (2–3 drinks per week).
His living mother was affected by type 2 diabetes; his
father died by accident at a young age, while a brother suf-
fered a myocardial infarction at age 43, seemingly not relat-
ed to traditional cardiovascular risk factors. The patient
weighed 79 kg and was 1.75 m tall (Body Mass Index,
BMI=25.8 kg/m2), and there had been no significant recent
weight modification. No significant abnormalities were
detected at physical examination.
Biochemical analyses (Table 1) corroborated the findings
of severe hypertriglyceridaemia (6.594 mg/dl), showing also
high cholesterol levels (658 mg/dl) and low plasma high-
density lipoprotein cholesterol (HDL-C, 15 mg/dl);
apolipoprotein A-I was 75 mg/dl and apolipoprotein B was
141 mg/dl, both within normal laboratory range. After refrig-
eration overnight at +4°C, serum showed a creamy surface
layer and a turbid infranatant, while lipoprotein elec-
trophoresis disclosed lipids at origin and a broad pre-β band:
both these tests indicated the presence of chylomicrons and
very low-density lipoproteins (VLDLs). Plasma creatinine
was within normal limits, while urinalysis detected trace
amounts of glucose and ketone bodies; liver and thyroid
functions were also normal; γ−glutamyl-transferase was
slightly increased and serum sodium decreased. Glucose
level (215 mg/dl) and glycated haemoglobin (HbA1c) were
increased, C-peptide was in the normal-high range, while
immune parameters were unaffected, in particular anti-
islet cells antibodies (ICA) and glutamic acid decarboxy-
lase antibodies (GADA) were not detected.
Preparative ultracentrifugation was carried out, showing
cholesterol enrichment in the density fraction <1.006 g/ml,
corresponding to chylomicrons+VLDLs. Apolipoprotein E
was homozygous for the most common isoform (ε3/ε3
genotype). We did not disclose a deficiency of apolipopro-
tein C-II, which represents the physiological lipoprotein
lipase (LPL) activator, but we could not directly evaluate
LPL activity.
Supra-aortic and lower limb echo-doppler examination
revealed increased intima-media thickness but no plaques,
while liver echotomography showed diffuse, high-grade
steatosis.
Along with clinical evaluation, dietetic therapy and a
four-injection insulin regimen was administered (3 short-act-
ing pre-prandial insulin, and one bedtime long-acting dose).
Treatment resulted in rapidly improving and rather steady
glycaemic control with progressive reduction of insulin
requirement. At the same time the dyslipidaemia was treated
with low-fat diet, subcutaneous calcium heparin (2000 IU,


Amino acid sequence homologies between HCV polyprotein and thyroid antigens

MARTOCCHIA A

FALASCHI, Paolo

Archivio della ricerca- Università di Roma La Sapienza

Amino acid sequence homologies between the HCV polyprotein and the thyroid antigens.

Czaja A et al

Interferon induced autoimmune thyroid disease (AITD): a model of human autoimmunity.

Interferon-alpha and autoimmune thyroid disease.

Susceptibility to thyroid disorders in hepatitis C. Clin Gastroenterol Hepatol 3:595–603

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Amino acid sequence homologies between HCV polyprotein and thyroid antigens

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