Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Out of 50 patients with sporadic amyotrophic lateral sclerosis (sALS), excluding 8 patients with recent immunosuppressive medication or low total IgG, we examined all available 92 sera of 11 women and 31 men nephelometrically for serum immunoglobulin concentrations including IgG isotypes IgG1-4. Mean serum levels of IgA and IgM remained within references in all cases. Isotypes IgG1 and IgG3 were the most frequently altered immunoglobulins. Without specific treatment, 34 out of 42 patients (= 80%) and 58 out of 92 sera (= 63%) demonstrated low IgG3 concentrations (< 0.41 g/l), while 14 patients (= 33%) and 20 sera (= 22%) demonstrated low IgG1 serum levels (< 4.22 g/l). In patients with normal total IgG, isotypes IgG1 and IgG2 often changed in a complementary way, and IgG1/IgG2 serum concentrations correlated significantly (rs = -0.518, P < 0.001). In four longitudinally monitored patients, the IgG3 isotype ranged from 1.3% to 8.2% of serum IgG and demonstrated a remarkable individual variability over time, corresponding to the relatively short half-life of IgG3. Since elevated circulating immune complexes may fluctuate rapidly, altered serum immunoglobulin isotypes could become more convenient parameters in a still enigmatic disease. To assess their role and relevance, their association with clinical course, cerebrospinal fluid and circulating immune complexes has to be examined.
 ...
PMID:Immunoglobulin-G isotype changes in human sporadic amyotrophic lateral sclerosis (ALS). 793 96

Of 25 male and 13 female patients diagnosed as sporadic cases of amyotrophic lateral sclerosis between 1989 and 1992, 17 had reproducible serum antibodies against human foamy virus (HFV = human spuma retrovirus, HSRV). HFV-positive ALS patients had higher IgG3 concentrations than HFV-negatives (P < 0.05) and competed better on maedi-visna retroviral antigen than HFV-negatives or controls (P < 0.05), but did not differ otherwise. Two HFV-positive patients were living in the same building; two other ALS patients lived within 300 m of one another, and three HFV gag reactive men (2 ALS, 1 control) were living in neighbouring villages. These were the closest geographic clusters found among current patients. We summarize recent findings compatible with a pathogenetic role for endogenous and/or exogenous retroviral sequences in adult motor neuron disease, and confirm a male preponderance as well as an inverse correlation between survival time and age at onset.
 ...
PMID:[Amyotrophic lateral sclerosis--indications of increased antiretroviral seroreactivity without obvious epidemiology]. 839 64

In order to get to clues about T-cell independent versus T-cell dependent immune mechanism in ALS, we measured IgG subclasses in 25 ALS-patients: 16 patients had deficiency of T-cell dependent expressed IgG1 or IgG3 or both with essentially normal levels of T-cell independent expressed IgG2 and IgG4. Ten of these patients had no prior treatment and five of these 10 had normal total IgG. Six patients had some immunosuppressive treatment before measurements of subclasses were done and all of them had deficiency of total IgG. Eight of 14 patients who underwent a d-xylose breath test, had evidence of small bowel overgrowth, which was confirmed by cultures of duodenal aspirate. IgG1 and IgG3 are T-cell dependent antibodies against protein antigens with close linkage on chromosome 14. The findings suggest a defect in the IgG subclass expression in ALS.
 ...
PMID:IgG subclass deficiency in amyotrophic lateral sclerosis. 847 88

We assessed humoral and cytokine responses in monthly plasma samples from ALS patients who received glatiramer acetate (GA) immunization every day or every other week, or remained untreated (control) from a six-month phase II trial. Samples were evaluated by GA-specific ELISA assays for detection of combined immunoglobulin (Ig) classes (IgM,A,G), IgG alone, and IgG subclasses (IgG1, IgG2, IgG3, and IgG4). T-helper (Th) type 1 and 2 (Th1 and Th2) cytokine levels were determined by flow cytometric cytokine bead arrays. Fourteen of 21 GA-immunized patients produced anti-GA Ig responses. Those treated every day produced anti-GA responses within one month, while those treated every other week exhibited responses by month two. All anti-GA IgG subclass concentrations were increased in excess of 4.2-fold in plasma from treated patients, and anti-GA IgG1 comprised the majority of the humoral response. Mean plasma cytokine levels were statistically indistinguishable between treatment regimens; however, stratification by patient and time on study showed more prevalent trends in changes of Th1 or Th2 cytokine levels following GA treatment every other week or every day, respectively. These data show significant humoral responses and cytokine trends following GA immunization in ALS patients.
 ...
PMID:Glatiramer acetate immunization induces specific antibody and cytokine responses in ALS patients. 1765 22

Amyotrophic lateral sclerosis may be an autoimmune disease. In this paper IgG subclasses levels in the CSF and sera and their intrathecal synthesis were studied. IgG subclasses levels were determined by ELISA method using monoclonal antibodies against human IgG subclasses, secondary biotinylated antibody and avidin-biotin-peroxidase complex. There was statistically significant elevation of IgG1 and IgG3 subclasses in the CSF of ALS patients. In sera of patients with ALS, IgG2 level was diminished, but there was no statistical difference in other IgG subclasses. IgG1 and IgG3 indices were elevated in patients with ALS, detecting synthesis of these subclasses in the CNS. General IgG index value did not differ from the control value. The results support the concept that autoimmune mechanisms may play a role in the pathogenesis of ALS.
 ...
PMID:IgG subclasses and their intrathecal synthesis in patients with amyotrophic lateral sclerosis. 2128 76