Tourtellotte's Formula Research Articles

Blood-brain-barrier and intrathecal immunoglobulin changes in tuberculous meningitis and demyelinating disorders: a preliminary report from a South Indian hospital

Sixty-three paired serum and CSF samples (15 controls and 48 patients) were studied for CSF albumin quotient, IgG index and synthesis rate. Control values for albumin quotient and IgG index were less than 10.0 and less than 0.6 respectively. IgG synthesis rate/day was calculated according to the Tourtellotte formula and a value of greater than 3.0 mg/day is considered high. Our findings in patients with central demyelinations, subacute sclerosing panencephalitis, Guillain Barré Syndrome and cerebrovascular accidents are comparable to earlier studies. Fifteen tuberculous meningitis patients were studied and could be separated into 2 groups, 9 with elevated albumin quotients and 6 with normal albumin quotients. Three patients with elevated albumin quotients and 4 with normal albumin quotients showed increased intrathecal IgG synthesis.

Relación entre el alelo HLA­DRB1*1501 y la gravedad de la esclerosis múltiple en una muestra de población española perteneciente a las Islas Baleares: influencia del sexo

There is some controversy about the possible relation between HLA-DR2 (DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602) and the severity of multiple sclerosis (MS), which could be due, at least in part, to methodological differences among the different studies dealing with this subject and/or to a lack of phenotypic homogeneity within the series of patients.This study aims to contribute information about the possible relation between DR2 (more specifically the HLA-DRB1*1501 allele) and the severity of MS.We conducted a study of 43 individuals with clinically defined MS, whose degree of severity was determined using Kurtzke's EDSS, and 107 controls from a similar ethnic origin. DETERMINATIONS: HLA typing by PCR-SSO and PCR-SSP, analysis of oligoclonal IgG bands in CSF by isoelectric focusing, and quantification of the intrathecal synthesis of IgG (IgG index, IgG ratio, Reiber's formula and Tourtellotte's formula).Chi2 test, Mann-Whitney test and Kendall correlation coefficient.DRB1*1501 is associated with the presence of MS only in females and with lower severity of the disease only in males. These associations do not appear to depend on any kind of effect exerted by DRB1*1501 on the intrathecal synthesis of IgG that differs between the two sexes.The absence of a relation between DRB1*1501 and the severity of MS reported in many studies could be due to not stratifying the patients according to sex. Our findings emphasise how important it is in genetic studies of complex traits to reduce the phenotypic heterogeneity of patients as much as possible.

Formulas for the quantitation of intrathecal IgG production: Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis

There are several formulas for the quantitative determination of intrathecal IgG production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these formulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) samples from 125 healthy individuals, 18–88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8–30); and 106 patients with definite multiple sclerosis (MS). The relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably linear in both healthy individuals ( r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF ( r = 0.95; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two formulas based on a nonlinear relation between the CSF/S albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values in the presence of BBB damage, probably because of incorrect constants in these formulas. There were no significant correlations between the CSF/S albumin ratio (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGGPROD, an empirical formula for the determination of intrathecal IgG production in mg/l. These results show that the IgG index, the Log IgG index and IGGPROD all give valid quantitative determinations of intrathecal IgG production even in the presence of BBB damage. The percentage of MS patients with a formula value higher than the mean + 2 SD of the control value was identical for the IgG index, the Log IgG index and IGGPROD (92%), and similar to the number of MS patients exhibiting OCBs in their CSF (96%). These results suggest that the quantitative determination of intrathecal IgG production is almost as sensitive as the qualitative detection of OCBs for demonstration of intrathecal IgG production.

Intrathecal synthesis of IgG subclasses in multiple sclerosis and in acquired immunodeficiency syndrome (AIDS)

Serum and cerebrospinal fluid (CSF) of 50 neurological patients (24 multiple sclerosis (MS), ten acquired immunodeficiency syndrome (AIDS) and 16 other neurological diseases (OND)) and ten controls were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgG subclass quantification and for the calculation of intrathecal synthesis (ITS). Total IgG was determined by two methods: electroimmunodiffusion (EID) and ELISA. A highly significant correlation was established between both methods. The existence of ITS was proved by the IgG/albumin ratio, the IgG index, Tourtellotte's formula, and Schuller's formula. In AIDS patients all IgG subclasses showed an increase in the CSF, whereas in sera only the IgG1 was significantly increased. CSF of MS patients showed a predominant increase of IgG1 whereas no significant modification of IgG subclasses was observed in sera. In most of the AIDS patients there was an ITS of IgG1, IgG3 and IgG4, but rarely (3/10) IgG2. In contrast, a polyclonal ITS of IgG was exceptional (1/24) in MS patients. No significant correlation could be established between clinical data and IgG subclass ITS in MS. The variations of each IgG subclass in serum and in ITS were not significantly correlated. Measurement of each IgG subclass and calculation of ITS seems essential in order to analyze any subclass antibody repertory inside the central nervous system.

Relative diagnostic value of cerebrospinal fluid kappa chains in MS

We used receiver operating characteristic (ROC) curve analysis to determine the relative performance of different CSF IgG parameters as diagnostic markers for multiple sclerosis. We quantitated CSF and serum IgG and albumin to determine an IgG albumin ratio, IgG index, Tourtellotte's synthesis rate, and Schuller's formula; CSF free kappa light chains were measured by radioimmunoassay. We compared a group of patients with clinically definite MS with a group of patients with a variety of other neurologic diseases. Tourtellotte's formula, IgG albumin ratio, IgG index, and free kappa chains distinguished the MS group from the comparative group of patients. ROC curve analysis demonstrated that CSF free kappa light chains were more closely linked to MS than the other measures. Multiple logistic regression analysis demonstrated no advantage of adding any single IgG measure or combination of measures to free kappa light chain analysis. Our results strongly suggest that free kappa light chains in CSF are the single best quantitative assay to support a clinical diagnosis of MS.

Muscle antibodies in the cerebrospinal fluid from patients with myasthenia gravis.

IgG antibodies to nicotinic acetylcholine receptor (AChR) and to a muscle antigen extracted by citric acid, were quantified in serum and cerebrospinal fluid (CSF) from 28 patients with myasthenia gravis, and the serum:CSF ratios compared with those of total IgG. Agarose-electrophoresis and calculations of the IgG index and Tourtellotte's formula were performed. No evidence of intrathecal antibody synthesis was demonstrated. Compared to the total IgG concentrations in serum and CSF, the CSF concentrations of IgG AChR antibodies were lower than expected.

Immunoglobulins in serum and cerebrospinal fluid from patients with acute Guillain-Barré syndrome.

IgG, IgA, IgM and IgE were quantified in serum and IgG and total protein were quantified in cerebrospinal fluid (CSF) from 80 patients with acute Guillain-Barré syndrome. The serum concentrations of IgM and IgA were significantly increased in approximately 25% of the patients, whereas the concentrations of IgG and IgE were normal. Increased CSF concentrations of IgG were found in more than 90% of the patients and correlated with increased CSF total protein concentrations. The CSF IgG/total protein ratio, CSF IgG index and Tourtellotte's formula were used to determine intra-thecal IgG synthesis in 30 of the patients. In eight of the patients the results of the CSF IgG index and Tourtellotte's formula were significantly increased, while in the remaining seven patients increased values were obtained using only one of these formulae. The CSF IgG/total protein ratio was normal in all the patients. Oligoclonal bands were not detected in any of the sera or CSF. Antibodies to peripheral nerve tissue were detected in approximately 30% of the patient sera, but could not be detected in the CSF.

On the diagnostic value of different CSF investigations in multiple sclerosis.

An assessment was made of the relative values of different methods of calculating intrathecal IgG synthesis in multiple sclerosis. In 60 patients with definite, probable or possible multiple sclerosis the IgG/protein and IgG/albumin ratios, the IgG index, the Tourtellotte formula and the graphic evaluation according to Reiber were applied. All the patients had oligoclonal IgG in the CSF. Reiber's method was the most sensitive, yielding 66% of abnormal findings. Only the cell count showed significant differences between active and inactive stages. There was a correlation between the cell count and the daily rate of intrathecal IgG synthesis and between the latter and the number of oligoclonal bands in CSF, but none of these parameters correlated with duration of disease or the number of previous bouts.

Isotachophoresis evaluation of synthesis of intrathecal IgG subfractions in multiple sclerosis.

Cerebrospinal fluid (CSF) and serum samples from patients with multiple sclerosis and other neurological diseases were examined by capillary isotachophoresis (ITP). The percentage and the rate of synthesis of CSF IgG which migrated slowly with ITP were calculated. CSF specimens of most patients with multiple sclerosis contained increased percentages of slowly migrating IgG (slow IgG), corresponding to IgG oligoclonal bands in the "high-alkaline" region on isoelectric focusing. The patients with multiple sclerosis were found to have increased intrathecal synthesis of slow IgG, which correlated closely with the rate of intrathecal CNS IgG synthesis calculated by Tourtellotte's formula.

Value of central nervous system IgG daily synthesis determination in the diagnosis of multiple sclerosis.

Using laser beam immunonephelometry, we confirmed the value of Tourtellotte's formula in the diagnosis of MS. Moreover, since immunonephelometry presents several advantages, including simplicity, rapidity, and precision, it is a promising technique for the diagnosis of MS. Complicated measurements are not necessary. Determinations take only minutes. The results are reproducible. Mathematics manipulations are simple with readily available computers.