Neuropsychiatric SLE Arises From Autoantibodies

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J a n u a r y 2 0 0 7 • w w w. r h e u m a t o l o g y n e w s . c o m Lupus/CT Diseases 23

Neuropsychiatric SLE Arises From Autoantibodies
Neuronal damage presents as cognitive and emotional compromised. “We’ve previously shown nephrine to simulate the adrenaline spike
that anti-DNA antibodies [which bind to associated with stress reactivity. In both
impairment in two-thirds of patients with lupus. double-stranded DNA and are highly as- cases, the autoantibodies were able to
sociated with SLE] will cross-react with reach the cerebral cortex and cause neu-
BY DIANA MAHONEY cular disease or telltale inflammation, said peptides, including one that is present on rocognitive symptoms.
Ne w England Bureau Dr. Diamond. In addition, in most studies, subunits of the NMDA [N-methyl-D-as- Of interest, according to Dr. Diamond,
the progressive cognitive impairment has partate] receptor,” said Dr. Diamond. The was the fact that the simulated infection
B O S T O N — Recent evidence linking au- not been associated with disease activity or NMDA receptor is expressed in neurons led to the death of nerve cells in the hip-
toantibodies to neuronal damage in sys- medication. throughout the brain and at a particular- pocampus while the simulated stress re-
temic lupus erythematosus suggests a new “When one thinks about the pathogen- ly high density in regions of the cerebral action attacked neurons in the amygdala.
paradigm for explaining the occurrence of esis of neuropsychiatric lupus, it’s logical cortex that are associated with learning The “regional specificity” of neuronal
cognitive and emotional impairment in pa- to consider vascular occlusion or hemor- and memory functions. The anti-DNA an- damage might explain variations in the na-
tients with the autoimmune disorder, ac- rhage associated with antiphospholipid tibodies bind to the NMDA receptors of ture and extent of cognitive and emo-
cording to Dr. Betty Diamond of Colum- antibodies. And one might also consider nerve cells in these regions and produce tional changes associated with neuropsy-
bia University in New York. cytokines, which in vitro can be toxic to apoptosis, she said. chiatric lupus, but it is the breach in the
Nearly two-thirds of patients with sys- neurons and alter neuronal function, but However, the damage can only occur if blood-brain barrier that sets the stage for
temic lupus erythematosus (SLE) experi- there has yet to be any correlation be- the blood-brain barrier is compromised. In the changes, she said.
ence neurologic and psychiatric symp- tween any particular cytokine in cere- studies with mice, “if the anti-DNA anti- The findings of these studies suggest “a
toms—referred to collectively as brospinal fluid (CSF) with any particular bodies did not permeate the blood-brain new paradigm for an immunologically
neuropsychiatric SLE—ranging from disease manifestation,” said Dr. Diamond. barrier, there were no behavioral or cog- mediated, noninflammatory loss of cog-
headaches, mild impairment of thinking, Medication, particularly steroids, could nitive changes,” said Dr. Diamond. In con- nitive function, not only in SLE but pos-
or personality changes to stroke, epilepsy, also be a contributing factor, although trast, when the barrier was broken, the an- sibly in other [autoimmune] conditions,”
and severe mental disorders. “And as our studies in lupus patients haven’t found tibodies bound to the areas of the brain said Dr. Diamond.
immunosuppressant therapies and arma- any correlation between either steroid involved in the regulation of emotion and In terms of clinical relevance, “blocking
mentarium of antibiotics has improved dose or duration with neuropsychiatric lu- memory, leading to cognitive and memo- the brain cell receptor to which the anti-
and lupus patients are living longer than pus, she said. ry impairment. This finding helps explain DNA antibodies bind could be a promis-
they used to, we’re seeing more of the late “Of course, one can’t think about lupus why antibody titers in the serum of lupus ing therapeutic option for neuropsychi-
sequelae of the disease and learning that without considering autoantibodies as part patients may not correlate with clinical atric SLE,” Dr. Diamond stated. In fact, in
cognitive dysfunction and disorders of ex- of the disease process, including the CNS symptoms of neuropsychiatric SLE and both of the aforementioned studies, the in-
ecutive function are major components of sequelae,” said Dr. Diamond, whose re- why, in the presence of serum antibody, vestigators demonstrated that immuniza-
disease morbidity,” Dr. Diamond reported cent research in this arena has borne symptoms may not progress, she said. tion with the NMDA agonist memantine
at a rheumatology conference sponsored promising fruit. In separate studies using mice with lu- (Namenda), which is used to treat
by Harvard Medical School. Specifically, Dr. Diamond and col- pus antibodies, Dr. Diamond and col- Alzheimer’s disease, protected the target-
The etiology of central nervous system leagues have determined that the loss of leagues forced open the blood-brain bar- ed neurons from damage and prevented
(CNS) involvement in lupus has long elud- cognitive function is likely immunologi- rier by injecting the bacterial endotoxin behavioral alterations, as did immuniza-
ed investigators, particularly because it cally mediated but only in individuals in lipopolysaccharide to simulate a mock tion with the D-isoform of the consensus
occurs without evidence of cerebral vas- whom the blood-brain barrier has been bacterial infection and by injecting epi- peptide. ■

Chorioretinopathy’s Autoimmune Etiology Limited to Eye
BY NANCY WALSH autoimmune disease, it would be one of
Ne w York Bureau the rare—and possibly the only—autoim-
mune disease that is restricted to one or-
S O R R E N T O , I T A LY — The posterior gan,” he said in an interview.
uveitis known as birdshot chorio- A longitudinal cohort study initiated by
retinopathy appears to be an eye-restrict- ophthalmologists at Cochin Hospital,
ed disease, reported Dr. Christian Pag- which is the French National Reference
noux at the Fifth International Congress Center for Vasculitides, provided the op-

C OURTESY D R . P R B RÉZIN /C OCHIN H OSPITAL /PARIS
on Autoimmunity. portunity for Dr. Pagnoux and his col-
In a careful assessment of the largest se- leagues from the French Vasculitis Study
ries to date of patients with birdshot Group to investigate disease manifesta-
chorioretinopathy—so named because of tions in 118 patients.
the distinct shotgun-like scatter pattern of Mean age was 51 years, and there was a
hypopigmented spots on the fundus— slight male predominance. Each patient
some were found to exhibit “intriguing” underwent a 30-minute medical interview
extraocular features, but there was no con- using a standardized report form, and data
vincing evidence of systemic involvement, on medical history before and after the on-
said Dr. Pagnoux of Cochin Hospital, Paris. set of birdshot chorioretinopathy were
Previous studies of birdshot chorio- collected.
retinopathy, in which patients complain of Among the study findings were that
floaters, blurred vision, nyctalopia, and 16% had drug allergies, 9% had asthma,
photophobia, have not addressed the pos- 8% had diabetes, and 10% had thyroid dis- Multiple distinctive hypopigmented lesions shown clustered around the optic disk:
sibility of patients having extraocular man- ease. One patient had antiphospholipid Retinal depigmentation reveals veins on transparency, and slight edema is visible.
ifestations despite the likelihood that the syndrome, three had Raynaud’s phenom-
disorder is autoimmune in nature. enon, and five reported a history of pso- flammation outside the eyes, such as ele- non–population control design and the
The evidence suggesting that birdshot riasis. In addition, 27% were hypertensive, vated C-reactive protein levels. “I think potential for recall bias. However, the use
chorioretinopathy is an autoimmune dis- and 14% had sinusitis. Hearing loss was one could say today, with a certain degree of standardized report forms by physicians
order includes a strong association with the reported by 7%. At the time of disease on- of confidence, that birdshot chorio- specializing in vasculitis may counterbal-
human leukocyte antigen (HLA)-A*29 set, 19% of patients also reported arthral- retinopathy is indeed an eye-restricted dis- ance these potential drawbacks, he said.
gene. Moreover, clinical features of the dis- gias, but none had arthritis or synovitis, ease,” he said. The study is ongoing, and patients will
ease resemble autoimmune S-antigen–in- Dr. Pagnoux said. Nonetheless, certain findings such as be re-evaluated every 5 years with the
duced uveoretinitis, and some patients have The incidence of these maladies is quite hearing loss, hypertension, and psoriasis goal of providing a clearer picture of the
granulomatous histology findings and fea- similar to those reported by the French are of interest and merit further attention natural history of the disease, particular-
tures associated with vasculitis, according general population, he said. “We also did as potential extraocular disease manifes- ly when macular edema occurs and visu-
to Dr. Pagnoux. “However, if it indeed is an not find any manifestations suggesting in- tations. Study limitations include the al acuity is lost. ■