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Autoimmunity Reviews 1 (2002) 329–337
HIV and autoimmunity
Gisele Zandman-Goddard, Yehuda Shoenfeld*
Center for Autoimmune Diseases, Department of Medicine ‘B’, Sheba Medical Center, Sackler Faculty of Medicine,
Tel-Aviv University, Tel-Hashomer 52621, Israel
Accepted 6 August 2002
Abstract
The association of immune dysfunction in patients with human immunodeficiency virus (HIV) infection and
AIDS and the development of autoimmune diseases is intriguing. Yet, the spectrum of reported autoimmune
phenomena in these patients is increasing. An infectious trigger for immune activation is one of the postulated
mechanisms and derives from molecular mimicry. During frank loss of immunocompetence, autoimmune diseases
that are predominantly T cell subtype CD8 driven predominate. There is evidence for B cell stimulation and many
autoantibodies are reported in HIV patients. We propose a staging of autoimmune manifestations related to HIVy
AIDS manifestations and the total CD4 count and viral load that may be beneficial in identifying the type of
autoimmune disease and establishing the proper therapy. In stage I there is the acute HIV infection, and the
immune system is intact. In this stage, autoimmune diseases may develop. Stage II describes the quiescent period
without overt manifestations of AIDS. However, there is a declining CD4 count indicative of some immunosuppression. Autoimmune diseases are not found. During stage III there is immunosuppression with a low CD4 count
and the development of AIDS. CD8 T cells predominant and diseases such as psoriasis and diffuse immune
lymphocytic syndrome (similar to Sjogren’s syndrome) may present or even be the initial manifestation of AIDS.
Also during this stage no autoimmune diseases are found. In stage IV there is restoration of immune competence
following highly active anti-retroviral therapy (HAART). In this setting, there is a resurgence of autoimmune
diseases. The frequency of reported rheumatological syndromes in HIV-infected patients ranges from 1 to 60%.
The list of reported autoimmune diseases in HIVyAIDS include systemic lupus erythematosus, anti-phospholipid
syndrome, vasculitis, primary biliary cirrhosis, polymyosits, Graves’ disease, and idiopathic thrombocytopenic
purpura. Also, there is an array of autoantibodies reported in HIVyAIDS patients which include anti-cardiolipin,
anti-b2 GPI, anti-DNA, anti-small nuclear ribonucleoproteins (snRNP), anti-thyroglobulin, anti-thyroid peroxidase,
anti-myosin, and anti-erythropoietin antibodies. The association of autoantibodies in HIV-infected patients to
clinical autoimmune disease is yet to be established. With the upsurge of HAART, the incidence of autoimmune
diseases in HIV-infected patients is increasing. In this review, we describe the various autoimmune diseases that
develop in HIVyAIDS patients through possible mechanisms related to immune activation.
䊚 2002 Elsevier Science B.V. All rights reserved.
Keywords: HIV; AIDS; Autoimmunity; Immune restoration; Autoantibodies
*Corresponding author. Tel.: q972-3-5302652; fax: q972-3-5352855.
E-mail address: [email protected] (Y. Shoenfeld).
1568-9972/02/$ - see front matter 䊚 2002 Elsevier Science B.V. All rights reserved.
PII: S 1 5 6 8 - 9 9 7 2 Ž 0 2 . 0 0 0 8 6 - 1
G. Zandman-Goddard, Y. Shoenfeld / Autoimmunity Reviews 1 (2002) 329–337
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Table 1
HIV and autoimmunity
Stage
Stage
description
CD4 count
Viral
load
AIDS
Autoimmunity
I
II
III
IV
Clinical latency
Cellular response
Immune deficiency
Immune restoration
High ()500)
Normalylow (200–499)
Low (-200)
High ()500)
High
High
High
Low
No
No
Yes
Controlled
Autoimmune disease
Immune-complex, vasculitis
Spondylo-arthropathy
Autoimmune disease
Autoimmune disease can occur with a preserved immune system requiring B and T cell interactions (normal CD4 count).
Therefore, autoimmunity is possible in Stages I, II and IV. With profound immunodeficiency (low CD4 count), autoimmune diseases
are not found. Stage IV (high CD4 count) describes HIV-infected patients with immune restoration, but possibly altered immunoregulation enabling the resurgence of autoimmune diseases.
1. Introduction
The combination of immune dysfunction in
patients with human immunodeficiency virus
(HIV) infection and AIDS and the development
of autoimmune diseases is intriguing. Yet, the
spectrum of reported autoimmune phenomena in
these patients is increasing w1,2x. This wide range
is due to different patient selection, and association
with the development of AIDS.
An infectious trigger for immune activation is
one of the postulated mechanisms in autoimmunity
and derives from molecular mimicry w3,4x. During
frank loss of immunocompetence, autoimmune
diseases that are predominantly T cell subtype
CD8 driven may predominate. Multiple anti-retroviral drug therapy for patients with AIDS provides
prolonged survival and immune restoration, a setting where autoimmune diseases develop. We propose a staging of autoimmune manifestations
related to HIVyAIDS manifestations and CD4
count that may be beneficial in identifying the
type of autoimmune disease and establishing the
proper therapy (Table 1). During Stage I there is
the acute HIV infection, and the immune system
is intact. In this stage, autoimmune diseases may
present. While Stage II is a quiescent period
without overt manifestations of AIDS, there is a
declining CD4 count indicative of some immunosuppression. Autoimmune diseases are not found.
During Stage III there is immunosuppression with
a low CD4 count. However, diseases where T cell
subtype CD8 predominant such as psoriasis and
diffuse immune lymphocytic syndrome (Sjogren’slike syndrome) may present or even be the initial
manifestation of AIDS. Autoimmune diseases are
not found. In Stage IV there is restoration of
immune competence following anti-retroviral therapy. In this setting, there may be a resurgence of
autoimmune diseases. In this review, we describe
the various autoimmune diseases that develop in
HIVyAIDS patients through possible mechanisms
related to immune activation.
2. Autoimmune diseases in HIV infection
The frequency of rheumatological syndromes in
HIV patients varies from less than 1 to 60% w2,5–
7x. The reported autoimmune diseases in HIVy
AIDS are reviewed.
2.1. Systemic lupus erythematosus
The unrestrained state of immune activation may
contribute to chronic inflammatory and autoimmune sequelae in HIV-infected individuals. Several
rheumatic entities, such as Reiter’s syndrome,
psoriatic arthritis, Sjogren’s-like syndrome,
myopathy and HIV-related vasculitis are often
correlated with the severity of the HIV infection
and improve with anti-retroviral therapy. However,
other entities, such as systemic lupus erythematosus (SLE) and sarcoidosis w8,9x, have a decreased
incidence in the HIV-infected population than
would be expected in the general population. This
inconsistency suggests that the immunosuppressive
effect of HIV may inhibit the development of
autoimmune diathesis. On the other hand, in a
setting of HIV infection that is controlled by
protease inhibitors and other anti-retroviral agents,
the immune system is no longer immunodeficient.
There is immune restoration with normalization of
G. Zandman-Goddard, Y. Shoenfeld / Autoimmunity Reviews 1 (2002) 329–337
the CD4 count and functional T cell reconstitution
w10x, so that a genetically predisposed host can
develop autoimmunity. This has been postulated in
the coexistence of HIV with SLE w11x. SLE may
be influenced by HIV type-1 infection. It has been
suggested that the immunosuppression resulting
from HIV infection can prevent the emergence of
SLE. There appear to be fewer cases of SLE in
the HIV-infected population than would be predicted, based on the overall incidence of SLE. To
date, 29 cases of association between the two
diseases have been reported, but the diagnosis was
simultaneous in just two of these and only 18
fulfilled the ARA criteria for the diagnosis of SLE.
Most patients experienced an improvement in their
SLE after development of their HIV associated
immunosuppression and a reactivation of lupus
manifestations has also been noted after immunological recovery secondary to anti-retroviral therapy w12x.
Fox and Isenberg w13x described a female patient
with SLE who was infected with HIV. Using stored
serum, the precise timing of HIV seroconversion
was determined and the early effects of HIV
infection on SLE examined. This infection resulted
in clinical improvement and the disappearance of
autoantibody production. On the other hand, Diri
et al. w14x reported a patient with HIV infection
who developed SLE after the initiation of highly
active anti-retroviral therapy (HAART).
A number of clinical and laboratory features of
HIV infection are found in SLE. Gonzalez et al.
w15x analyzed the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP)
in both diseases. Sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE,
and from 50 healthy children were studied. Results
included the detection of anti-snRNP antibodies
by ELISA in 30 HIV-infected patients (68.1%)
and 19 SLE patients (86.3%). These antibodies
were directed against U1-RNP (61.3 and 77.2%,
respectively), Sm (29.5 and 54.5%, respectively),
60 kDa RoySS-A (47.7 and 50%, respectively),
and LaySS-B proteins (18.1 and 9%, respectively).
None of the HIV-infected children and 11 SLE
patients (50%) showed anti-snRNP antibodies by
counter immunoelectrophoresis. None of the HIVinfected patients showed anti-70 kDa U1-RNP or
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anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted on
the presence of non-precipitating anti-snRNP antibodies. No such reactivities were observed among
the normal sera tested. The authors concluded that
non-precipitating anti-snRNP antibodies in HIVinfected children are as frequent as in childhoodonset SLE. The significance of these antibodies is
not clear at present. Although polyreactive and
low-affinity antibodies and a mechanism of molecular mimicry may explain these results, a specific
stimulation of B cells by nuclear antigens could
not be excluded. Review of the literature revealed
that rheumatologic signs and symptoms were common in HIV and overlapped significantly with
SLE. Autoantibodies also occurred frequently in
both diseases.
2.2. Anti-phospholipid syndromeyanti-cardiolipin
antibodiesyanti-b2 GPI antibodies
In 1992, the association of anticardiolipin (aCL)
antibodies with HIV infection in male homosexuals was reported w16x. Since then, many studies
have alluded to this specific combination w17–20x.
We described an unusual presentation of antiphospholipid syndrome (APS) associated with acute
HIV infection. The APS in this patient was characterized by elevated titers of aCL antibodies and
anti-b2 GPI, necrotic lesions in the lower extremities and testicular necrosis requiring orchiectomy.
The patient had no history of AIDS, no previous
opportunistic infections, and was not on any retroviral medications. The CD4 count was only minimally decreased (CD4-322) indicating that the
patient had an acute infection and was not immunosuppressed w17x.
The aCL antibodies described in HIV patients
are of both the pathogenic type (b2 GPI cofactor
dependent) and the infectious type (non-b2 GPI
dependent). It seems that following infections, one
may see both types of aCL as well as all isotypes
and diversity of aCL including anti-PS w21x. Antiphospholipid antibodies have previously been
detected in HIV patients. The presence of lupus
anticoagulant (LA), aCL antibodies, anti-prothrombin antibodies, and anti-b2 GPI antibodies
were investigated in 61 HIV patients and 45
patients with APS. LA was present in 72% of HIV
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patients and 81% of APS patients. Anti-cardiolipin
antibodies were detected in 67% of the HIV
patients and 84% of APS patients. The detection
of anti-prothrombin and anti-b2 GPI antibodies
was significantly less in HIV patients w21x. Petrovas et al. w19x investigated the phospholipid specificity, avidity, and reactivity with b2 GPI in 44
patients with HIV infection and compared to the
results in 6 SLE patients with secondary APS, 30
SLE patients without APS, and 11 patients with
primary APS. Interestingly, the prevalence of aCL,
anti-phosphotidyl serine, anti-phosphotidyl inositol, and anti-phosphotidyl choline (36%, 56%,
34% and 43%, respectively) was similar to that
found in the SLEyAPS and primary APS patients.
The prevalence of these antibodies was significantly higher than that observed in SLEynon-APS
patients. Anti-b2 GPI antibodies occurred in only
5% of HIV-1 infected patients. A significant
decrease of aPL binding after treatment with urea
and NaCl was observed in the sera of HIV-1
infected patients when compared to APS patients,
indicating that aCL antibodies from HIV patients
have low resistance to dissociating agents. Guerin
et al. w22x investigated anti-b2 GPI antibody isotype and IgG subclass in APS patients and a
variety of other thrombotic and non-thrombotic
disorders including infections. Elevated levels of
IgM anti-b2 GPI antibodies were observed in 65%
of patients with APS and 27% of patients with
HIV infection.
In another study, Guglielmone et al. w23x investigated the distribution of aCL isotypes and
requirement of protein cofactor in viral infections
including HIV. The isotype distribution of aCLs in
the sera from 40 patients with infection caused by
HIV-1 was studied by ELISA in the presence and
absence of protein cofactor (mainly b2-GPI). The
prevalence of one or more aCL isotypes in serum
of patients with HIV-1 infection was 47%. Most
of these antibodies were mainly cofactor
independent.
2.3. Autoimmune thrombocytopenia
Immune thrombocytopenic purpura (ITP)
occurs in as many as 40% of patients infected
with the HIV. Aboulafia et al. sought to evaluate
the effect of HAART on platelet counts in 11
homosexual men with HIV-associated ITP patients.
At initial evaluation, 7 patients were anti-retroviral
naive, 2 were taking zidovudine alone, and 2
were receiving combination anti-retroviral therapy
for known HIV infection. For 6 patients with
-30=109 platelets, prednisone was initially coadministered with HAART. The primary outcome
measure was the platelet count response to
HAART, which was measured weekly until counts
had normalized on 3 consecutive occasions, then
every 3 months while on HAART. Secondary
outcome measures were HIV-viral RNA levels and
CD4q cell counts. The results were that 1 month
after the initiation of HAART, 10 patients had an
increase in mean platelet count. This improvement
was sustained at 6 and 12 months’ follow-up for
9 of 10 patients. Increases in mean platelet count
at 6 and 12 months of the 9 responders were
statistically significant. The range of follow-up in
the 9 responders was 21–46 months (median, 30
months), with no thrombocytopenic relapses. The
9 long-term platelet responders were maintained
on HAART and at 12 months had a mean reduction
of )1.5 log 10 in HIV-viral RNA serum levels
and a marked improvement in CD4q T-lymphocyte
cell count. HAART seems to be effective in
improving platelet counts in the setting of HIVassociated ITP, enhancing CD4q cell counts, and
reducing HIV viral loads w24x.
2.4. Vasculitis
Different types of vasculitis are associated with
HIV infection. Co-infections inducing vasculitis
have been reported, including hepatitis B and C.
Systemic necrotizing vasculitis, leukocytoclastic
vasculitis, cryoglobulinemia, and CNS vasculitis
have been reported w2,25,26x. Panarteritis nodosum
more frequently affects the neuromuscular system
and skin. Antineutrophilic cytoplasmic antibodies
are found less commonly. Vasculitis of the peripheral nerve may cause mononeuritis multiplex or
polyneuropathy, sometimes the presenting symptom of HIV infection or after the development of
AIDS w26x. HIV antigens and HIV-particles can
be identified by electron microscope and positive
in situ hybridization studies for HIV have been
reported in perivascular cells w2x.
G. Zandman-Goddard, Y. Shoenfeld / Autoimmunity Reviews 1 (2002) 329–337
Acute coronary vasculitis resulting in a fatal
myocardial infarction in a 32-year-old HIV patient
without coronary heart disease risk factors was
reported. Histological analysis of two coronary
arteries on autopsy showed a dense infiltration of
lymphocytes with necrosis of the intima. In situ
hybridization showed sparse intense staining indicating the presence of HIV-1 sequences within the
arterial wall w27x.
2.5. Polymyositis and dermatomyositis
HIV-associated polymyositis was first described
in 1983, and many reports in the past several years
confirm this association w2,28x. Dermatomyositis
is also seen in HIV infection w29x. The clinical
course, laboratory and electromyography findings
are similar to the idiopathic form w2x.
2.6. Thyroid diseaseyGraves’ diseaseyanti-thyroglobulin
antibodiesyanti-thyroid
peroxidase
antibodies
Jubault et al. w30x analyzed the kinetics of CD4
cells, HIV viral load, and autoantibodies in AIDS
patients with Graves’ disease after immune restoration on (HAART). Five patients were diagnosed with Graves’ disease after 20 months on
HAART, several months after the plasma HIV
viral load was undetectable, and when the CD4
count had risen from 14 to 340=106 cellsyl Antithyroid peroxidase (anti-TPO) and anti-TSHR
antibodies appeared 14 months after starting
HAART and 12 months after the rise in the CD4
count. No other autoantibodies were detected. The
autoantibodies were not detected in HIV-1 patients
without hyperthyroidism.
2.7. Primary biliary cirrhosis
Mason et al. w31x used immunoblots as a surrogate test to find out whether retroviruses play a
part in the development of primary biliary cirrhosis. Western blot tests were performed for HIV-1
and the human intracisternal A-type particle
(HIAP), on serum samples from 77 patients with
primary biliary cirrhosis, 126 patients with chronic
liver disease, 48 patients with SLE, and 25 healthy
volunteers. HIV-1 p24 gag seroreactivity was
found in 27 (35%) of 77 patients with primary
biliary cirrhosis, 14 (29%) of 48 patients with
333
SLE, 14 (50%) of 28 patients with chronic viral
hepatitis, and 9 (39%) of 23 patients with either
primary sclerosing cholangitis or biliary atresia,
compared with only one (4%) of 24 patients with
alcohol-related liver disease or a1-antitrypsin-deficiency liver disease, and only 1 (4%) of 25 healthy
volunteers (Ps0.003). Western blot reactivity to
more than two HIAP proteins was found in 37
(51%) of patients with primary biliary cirrhosis,
in 28 (58%) of patients with SLE, in 15 (20%)
of patients with chronic viral hepatitis, and in 4
(17%) of those with other biliary diseases. None
of the 23 patients with either alcohol-related liver
disease or a1-antitrypsin-deficiency, and only one
of the healthy controls showed the same reactivity
to HIAP proteins (P-0.0001). The results showed
a strong association between HIAP seroreactivity
and the detection of autoantibodies to doublestranded DNA. HIAP seroreactivity was also
strongly associated with the detection of mitochondrial, nuclear, and extractable nuclear antigens.
The HIV-1 and HIAP antibody reactivity found in
patients with primary biliary cirrhosis and other
biliary disorders may be attributable either to an
autoimmune response to antigenically related cellular proteins or to an immune response to uncharacterized viral proteins that share antigenic
determinants with these retroviruses.
2.8. Other autoimmune diseases
Other reported diseases include Raynaud’s phenomenon and Behcet’s disease. The prevalence of
these disorders is not known w32,33x.
3. Autoantibodies in HIV infection
The array of autoantibodies reported in HIVy
AIDS patients is found in Table 2. In a prospective
study of 100 sequentially selected HIV-infected
patients, the frequency and specificity of autoantibodies in HIV-infected subjects and their association with rheumatic manifestations, immunodeficiency, total CD4q cell count and prognosis
was evaluated. Patients were followed for 2 years.
HIV-infected patients presented high overall frequency of autoantibodies. No difference was
observed between immunodeficient and asymptomatic HIV-infected patients. The most frequent
specificities were antibodies to cardiolipin and to
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G. Zandman-Goddard, Y. Shoenfeld / Autoimmunity Reviews 1 (2002) 329–337
Table 2
Autoantibodies in HIV
Autoantibody
Disease
Frequency
Reference
Anti-a myosin
Anti-EPO
Anti-TPO
Anti-TSHR
Anti-cardiolipin
Anti-PS
Anti-PI
Anti-PC
Anti-b2 GPI
Anti-prothrombin
Anti- DNA
ANTI-snRNP
Left ventricular dysfunction
Anemia
Grave’s disease
Grave’s disease
APS
APS
APS
APS
APS
43%
23.5%
5 patients
5 patients
1 patient
56%
34%
43%
5–27%
w35x
w36x
w30x
w30x
w17x
w19x
w19x
w19x
w19,22x
w22x
w34x
w15x
68.1%
APS, antiphospholipid syndrome; EPO, erythropoietin; NG, not given.
denatured DNA. Immunoglobulin serum levels did
not correlate with the occurrence of autoantibodies.
Rheumatic manifestations were observed in 35y
100 HIV-infected patients and were not associated
with the occurrence of autoantibodies or the presence of immunodeficiency. The presence of autoantibodies was significantly associated with lower
CD4q lymphocyte counts and increased mortality,
which implies prognostic significance to this phenomenon in the context of HIV infection w34x.
3.1. Cardiac autoimmunityyanti-myosin autoantibodies
Currie et al. w35x investigated the frequency of
circulating specific autoantibodies in 74 HIV positive patients with and without echocardiographic
evidence of left ventricular failure. Abnormal antia myosin autoantibody concentrations were found
more often in HIV patients with heart disease
(43%) than in HIV positive patients without heart
disease (19%) or in HIV negative controls (3%).
The data support a role for cardiac autoimmunity
in the pathogenesis of HIV related heart muscle
disease.
3.2. Anemiayanti-erythropoietin antibodiesyautoimmune hemolytic anemia
In a cohort of 204 unselected consecutive HIV1 infected patients, the association of circulating
autoantibodies to endogenous erythropoietin
(EPO) with HIV-1 related anemia was studied.
Circulating autoantibodies to EPO were present in
48y204 (23.5%) of the patients. The circulating
autoantibodies were an independent predictor of
anemia. Autoimmunity may contribute to the pathogenesis of HIV-1 related anemia w36x.
In addition, autoimmune hemolytic anemia
(HIV-AIHA) was described in 4 men diagnosed
with HIV infection (AIDS). All patients presented
with the acute onset of severe hemolytic anemia,
fever, and splenomegaly. The direct and indirect
antiglobulin tests were positive in all, and 3
patients had mixed warm and cold autoantibody
hemolytic anemia. Two patients responded to prednisone therapy and remained in remission from
AIHA for 15 and 30 months, respectively w37x.
3.3. Mechanisms
The possible mechanisms for autoimmune manifestations of HIV infection include the direct
effect of HIV on endothelial, synovial, and other
hematopoietic cells resulting in destruction of CD4
cells, increased cytotoxic cell activity, and
increased expression of autoantigens.
Molecular mimicry is one of the proposed mechanisms in the development of autoimmune disease.
The exogenous infectious agent may have molecular similarity to a self-antigen and may therefore
induce an autoimmune response. The basis for this
mechanism has been substantiated in several studies. Deas et al. w38x previously demonstrated that
about one-third of patients with either Sjogren’s
G. Zandman-Goddard, Y. Shoenfeld / Autoimmunity Reviews 1 (2002) 329–337
335
Fig. 1. Autoimmune disease may develop in HIV-infected patients parallel to normal CD4 count (Stage I, II). Once the CD4 count
decreases past a threshold, autoimmune disease is not present (Stage III). Following HAART, a rise in the CD4 count above the
threshold enables autoimmune disease to emerge (Stage IV).
syndrome (SS) or SLE react to HIV p24 core
protein antigen without any evidence of exposure
to, or infection with, HIV itself. They further
characterized the specificity of this reaction using
enzyme-linked immunosorbent assay to peptides
representing fragments of p24. Characteristic epitope-specific profiles were seen for SS and SLE
patients. SS patients had significantly increased
responses to peptides F (p24 amino acids 69–86)
and H (amino acids 101–111) and diminished
reactivity to peptides A (amino acids 1–16) and
P (amino acids 214–228). SLE patients had
increased reactivity to peptides E (amino acids
61–76), H, and P. Utilization of peptide P hyporeactivity as the criterion to select for SS patients
results in a screen that is moderately sensitive
(64%) and specific (79.3%). Adding hyperreactivity to one other peptide (F or H) as an additional
criterion yields an expected decrease in sensitivity
(to 41%) while increasing specificity (to 93.1%).
All sera-reactive peptides from regions of known
structure of HIV p24 were located in the apex of
the p24 molecule. Thus, the specificity of the
peptide reactivities described indicates a specific
pattern of a nonrandom cross-reactivity between
HIV type 1 p24 and autoimmune sera, which may
be partially syndrome specific.
Autoimmunity during HIV-1 infection may contribute to the immunopathogenesis of AIDS. Titers
of autoantibodies to HLA molecules and other
surface markers of CD4q T cells appear to increase
with the progression of disease and may correlate
with lymphopenia. Other autoantibodies are directed at a number of regulatory molecules of the
immune system. Genesis of autoreactivity may be
related to structural homologies of HIV-1 envproducts, to such functional molecules involved in
the control of self-tolerance. The most impressive
similarities include the HLA-DR4 and -DR2, the
variable regions of TCR a-, b- and g-chain, the
Fas protein, and several functional domains of IgG
and IgA. Thus, HIV-1 infection may induce dysregulation leading to autoimmune response,
through a number of molecular mimicry mechanisms. Pathogenicity of antibodies to T cells could
also include the activation of membrane-to-nucleus
signal transducers resulting in increased apoptosis.
The evolution of autoimmune mechanisms during
HIV-1 infection cannot exclude, however, progression to immunoproliferative malignancy, since
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aspects of oligoclonal immune response to HIV-1
components may occur in several autoimmune
diseases, which in some instances evolve to lymphoma w39x.
In summary, autoimmune diseases and autoantibodies are present in HIV infection. Autoimmune
diseases may develop during acute viral infection
(Stage I), with normal to low CD4 counts (Stage
II). However, past a threshold where the CD4
count is profoundly low, autoimmune disease cannot develop (Stage III). Following HAART,
immune restoration (normal CD4 count) with possible altered immune regulation may lead to the
emergence of autoimmune diseases (Stage IV)
(Fig. 1). More studies are necessary to identify
the subgroups of HIV-infected patients that may
be prone to develop autoimmune diseases and
autoantibodies.
Take-home messages
● Autoimmune diseases may occur in patients
with HIV infection.
● We propose a staging of HIVyAIDS by clinical
manifestations, and CD4 count to assess the
concurrence with autoimmue diseases.
● Autoimmune diseases occur when there is no
immunosuppression such as during acute infection (Stage I), when the CD4 count )200
(Stage II), or following highly active antiretroviral therapy (Stage IV). Autoimmune disease is not reported in patients with profound
immunosuppression (Stage III).
● Reported autoimmune diseases in the setting of
HIV infection include SLE, anti-phospholipid
syndrome, autoimmune thrombocytopenia, vasculitis, polymyositis, Graves’ disease, and primary biliary cirrhosis.
● Autoantibodies in HIV infected patients are
diverse.
● Molecular mimicry may be a possible
mechanism.
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