Infection-associated decrease of serum creatine kinase levels in Fukuyama congenital muscular dystrophy.

BACKGROUND: Marked decreases in serum creatine kinase levels have been noted in Duchenne and Becker muscular dystrophies as rare complications of autoimmune or autoinflammatory diseases. SUBJECTS AND METHODS: The influence of systemic inflammation on serum creatine kinase levels was reviewed from the charts of three subjects with Fukuyama congenital muscular dystrophy. RESULTS: A total of 30 infectious events were identified. Elevated serum C-reactive protein levels coincided with decreased creatine kinase levels on 19 occasions. In one subject, administration of 2 mg/kg/d prednisolone for bronchial asthma resulted in a decrease in creatine kinase level on six other occasions. CONCLUSION: Apart from an increase in endogenous cortisol secretion, certain inflammation-related molecules could play a role in mitigating muscle cell damage in Fukuyama congenital muscular dystrophy during febrile infectious episodes. Corticosteroids may be a promising agent for the treatment of muscular symptoms in this disorder.

Alport syndrome-like basement membrane changes in Frasier syndrome: an electron microscopy study.

Frasier syndrome (FS) is a rare disease characterized by male pseudohermaphroditism and slowly progressing nephropathy. FS originates from heterozygous mutation in the intron 9 splicing donor site of Wilms' tumor suppressor gene (WT1). Focal segmental glomerular sclerosis is common in FS, but there have not been so many detailed pathologic investigations. The authors examined the kidneys of 3 patients with FS. The results showed that nephropathy started as mesangial proliferative glomerulonephritis, and later a concomitant focal segmental lesion developed. In all cases, electron microscopy results showed widespread thinning, splitting, and lamellation of the glomerular basement membrane, which mimicked hereditary nephritis. Throughout adulthood, WT1 protein expresses on glomerular podocytes. Recent reports described that podocytes expressing WT1 play an important role in maintaining the glomerular basement membrane. Hereditary nephritis-like glomerular basement membrane findings in FS suggest that one of the important functions of podocytes is to form and maintain the glomerular basement membrane.

Acute disseminated encephalomyelitis and poststreptococcal acute glomerulonephritis.

We experienced the case of a boy suffering from acute disseminated encephalomyelitis and concomitant acute glomerulonephritis. The multiple lesions observed on MR images, which located mainly in the cortical gray matter, quickly responded to methyl prednisolone pulse therapy. Renal biopsy confirmed the diagnosis of poststreptococcal acute glomerulonephritis. Streptococcus pyogenes was identified by pharyngeal culture, and the infection was serologically confirmed. We speculated that S. pyogenes infection was coincidentally involved in both diseases.

Latent cerebral hypoperfusion in a boy with persistent nephrotic syndrome.

Pediatricians are often faced with both bad temper and decreased daily activity in children with persistent nephrotic syndrome. These problems, which might affect both mental and physical development, have been explained as a consequence of general fatigue due to systemic edema and/or long-term hospitalization. However, other factors, such as cerebral hypoperfusion, may be involved. We experienced a case of a boy with steroid-resistant nephrotic syndrome who showed diffuse cerebral hypoperfusion on single photon emission computed tomography. Diffuse cerebral hypoperfusion dramatically resolved as the nephrotic syndrome remitted. His bad temper, decreased daily activity, and delay of speech and motor development also improved. In our patient, cerebral hypoperfusion might have been associated with his mental problems, physical problems, and delayed development of speech.

The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells.

Treatment with synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) is remarkably protective against otherwise lethal infection. Here, we describe an essential role for the transcription factor T-bet in mediating the protective function of CpG ODNs. Loss of T-bet in conventional CD11c(hi) dendritic cells (DCs) and in plasmacytoid DCs impaired production of IFNs. Strikingly, in contrast to Rag2-/- mice, Rag2-/- mice that also lacked T-bet (DKO) could not be rescued from lethal Listeria monocytogenes infection by prior treatment with CpG ODN. Rescue was achieved by adoptive transfer of CD11c(hi) DCs from WT, but not T-bet-/-, CpG ODN-treated donor mice. We conclude that T-bet in DCs is required for the adjuvant activity of CpG ODN in infection, revealing its vital role in innate immunity.

Suppressive oligonucleotides protect against collagen-induced arthritis in mice.

OBJECTIVE: To examine whether systemic administration of oligonucleotides (ODNs), known to inhibit the production of proinflammatory cytokines, alters host susceptibility to collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA). METHODS: CIA was induced by injecting DBA/1 mice with type II collagen (CII) in Freund's complete adjuvant, followed 3 weeks later by CII in Freund's incomplete adjuvant. The effect of suppressive ODNs on the incidence and severity of disease was monitored, as were immune correlates of CIA. RESULTS: Suppressive ODNs administered during the inductive phase of CIA significantly reduced the incidence and severity of arthritis. Treatment with suppressive ODNs significantly decreased serum titers of pathogenic IgG anti-CII autoantibodies and interferon-gamma production by collagen-reactive T cells. CONCLUSION: Suppressive ODNs may be of therapeutic value in the treatment of RA, and potentially other autoimmune diseases.

CpG oligodeoxynucleotides improve the survival of pregnant and fetal mice following Listeria monocytogenes infection.

Listeria infection during pregnancy can cause the death of both mother and fetus. Previous studies established that immunostimulatory CpG oligodeoxynucleotides (ODN) increase the resistance of healthy adult mice to many infectious pathogens, including Listeria monocytogenes. This study examines whether the innate immune response elicited by CpG ODN can reduce the susceptibility of pregnant mice to lethal listeria challenge. The results indicate that CpG ODN treatment significantly improves maternal survival and reduces pathogen transmission to offspring. CpG ODN administered during pregnancy did not induce abortion, birth defects, or reduce the size or health of litters. These findings suggest that CpG ODN may provide a safe and effective means of improving the health of mothers and fetuses during pregnancy.

Mizoribine as an effective combined maintenance therapy with prednisolone in child-onset systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is one of the major collagen diseases in childhood. However, the pathogenesis of this disease still remains unknown. The disease is known as a chronic inflammatory disease. Since oral and intravenous corticosteroid therapy has been introduced into the treatment of SLE, the prognosis of patients has improved significantly. However, it has now become clear that there are limitations in the effectiveness, as well as adverse reactions when corticosteroids therapy is administered for a long-term period. Therefore, we have been attempting to improve the maintenance therapy of child-onset SLE. METHODS: We have proposed and tested a new type of combination therapy using prednisolone (PSL) and mizoribine (MZR) in pediatric patients with SLE for maintenance therapy after the induction of remission. RESULTS: Our results showed that this combination therapy is more effective than the previous regimen. In addition, no significant side-effects were observed in our study. CONCLUSION: This combination therapy is still not perfect. Efforts should be continued to establish an optimal therapy regimen for child-onset SLE.