Research Notes: Lupus and Prader-Willi Syndrome

Lupus. 2007.
Cardiac tamponade due to systemic lupus erythematosus in patient with Prader-Willi syndrome after growth hormone therapy.
Kuramochi Y, Kato T, Sudou M, Sugano H, Takagi H, Morita T.

We present a 16-year old girl with Prader-Willi syndrome who developed cardiac tamponade as an initial finding of systemic lupus erythematosus. Until one year prior to this episode, she had received growth hormone treatment for nine years. The association among Prader-Willi syndrome, growth hormone treatment and systemic lupus erythematosus is discussed.

Ann N Y Acad Sci. 2007 Jun.
DNA methylation and systemic lupus erythematosus.
Balada E, Ordi-Ros J, Vilardell-Tarrés M.
Research Unit in Systemic Autoimmune Diseases, Vall d'Hebron Research Institute, Hospital Vall d'Hebron, Barcelona, Spain.

Several studies have indicated the importance of DNA hypomethylation in the etiology of systemic lupus erythematosus (SLE). Different enzymes linked to the DNA methylation process have been described. The identification of all these enzymes means that cells have the capacity to modify their methylation patterns. Therefore, to obtain a deeper understanding of the role this epigenetic mechanism may have on SLE, the enzymes involved in the DNA methylation mechanism must be thoughtfully analyzed. In fact, studies of enzymes (other than DNMT1) in this autoimmune disease are still lacking. We have recently investigated the simultaneous gene expression of DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4 in SLE patients. Here we review some of the studies that focus on the relationship between DNA methylation and SLE as well as we report our recent findings in this field. We suggest some alternative hypothesis that could help to understand the causes of the global DNA hypomethylation observed in the CD4+ T cells of these patients.

Immunity. 2007 Aug.
Mammalian N-Glycan Branching Protects against Innate Immune Self-Recognition and Inflammation in Autoimmune Disease Pathogenesis.
Green RS, Stone EL, Tenno M, Lehtonen E, Farquhar MG, Marth JD.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.

Autoimmune diseases are prevalent and often life-threatening syndromes, yet the pathogenic triggers and mechanisms involved remain mostly unresolved. Protein asparagine linked- (N-) glycosylation produces glycan structures that substantially differ among the extracellular compartments of evolutionarily divergent organisms. Alpha-mannosidase-II (alphaM-II) deficiency diminishes complex-type N-glycan branching in vertebrates and induces an autoimmune disease in mice similar to human systemic lupus erythematosus. We found that disease pathogenesis provoking glomerulonephritis and kidney failure was nonhematopoietic in origin, independent of complement C3 and the adaptive immune system, mitigated by intravenous administration of immunoglobulin-G, and linked to chronic activation of the innate immune system. N-glycans produced in alphaM-II deficiency bear immune-stimulatory mannose-dependent ligands for innate immune lectin receptors, disrupting the phylogenic basis of this glycomic recognition mechanism. Thus, mammalian N-glycan branching safeguards against the formation of an endogenous immunologic signal of nonself that can provoke a sterile inflammatory response in the pathogenesis of autoimmune disease.

Arq Neuropsiquiatr. 2007 Jun.
A study of T CD4, CD8 and B lymphocytes in narcoleptic patients.
Coelho FM, Pradella-Hallinan M, Alves GR, Bittencourt LR, Pedrazzoli Neto M, Moreira F, Tufik S.
Sleep Disorders Institute, EPM, UNIFESP, São Paulo, SP, Brazil.

Narcolepsy is characterized by excessive daytime sleep and cataplexy. Little is known about the possible difference in pathophysiology between patients with or without cataplexy. OBJECTIVE: To quantify T CD4, T CD8 and B lymphocytes in subgroups of patients with narcolepsy and the presence or absence of the HLA-DQB1*0602 allele between groups. METHOD: Our study was prospective and controlled (transversal) with 22 narcoleptic patients and 23 health control subjects. Patients underwent an all-night polysomnographic recording (PSG) and a multiple sleep latency Test (MSLT). The histocompatibility antigen allele (HLA-DQB1*0602), T CD4, CD8 and B lymphocytes were quantified in control subjects and in narcoleptics. RESULTS: The HLA-DQB1*0602 allele was identified in 10 (62.5%) of our 16 cataplexic subjects and in 2 (33.3%) of the 6 patients without cataplexy (p=0.24). In control subjects, HLA-DQB1*0602 allele was identified in 5 (20%). A significant decrease in T CD4 and B lymphocytes was found in narcoleptic patients with recurrent cataplexy when compared with our patients without cataplexy. CONCLUSION: Autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis were associated with a decrease in sub-group of T CD4 and B lymphocytes. A drop in B lymphocytes count in reumathoid arthritis might, it is posited, be correlated to the presence of HLA-DRB1 allele along with an overall worsened outcome of the affliction. The theory of an increase in consumption of B lymphocytes over the maturation phase has likewise been put forward. Our study reinforces the view that narcolepsy should be considered from an immunological perspective.