Free kappa and lambda light chain levels in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases.

Free kappa and lambda light chains were assayed by particle-counting immunoassay in cerebrospinal fluid (CSF) from patients with various neurological disorders. Detection limits were 25 and 50 ng/ml, respectively. Values of free kappa chain were higher than 50 ng/ml (upper reference limit) in 155 of 191 (81%) multiple sclerosis (MS) patients, in 100 of 168 (60%) patients with central nervous system (CNS) infections but in 41 of 217 (19%) patients with other neurological disorders. Free kappa chains were also assayed in 273 matched sera. The mean concentration in the control group (1.58 micrograms/ml; SD: 0.41) did not differ significantly from those in MS sera (1.63 micrograms/ml; SD: 0.43). The free kappa chain index was increased in 86% of MS patients and in 40% of patients with CNS infections. Regarding free lambda chains, CSF values were higher than 240 ng/ml (upper reference limit) in most neurological disorders (50-100%). However, the use of a lambda chain index increased the specificity of the assay as this index was higher than the upper reference value in 86% of MS patients and in only 23% of patients with infectious diseases. In MS, high levels of free kappa and lambda indices correlated significantly (P less than 0.01) with either the presence of oligoclonal bands or a high IgG index. Local synthesis of free light chains is an additional marker of an ongoing immune response within the CNS, especially in MS.

Particle counting immunoassay of S100 protein in serum. Possible relevance in tumors and ischemic disorders of the central nervous system.

S100 protein (S100) was assayed by particle counting immunoassay in serum samples from 50 healthy individuals, 325 patients with various neurological disorders, and 20 patients with malignant melanoma. The detection limit for this protein was 0.3 microgram/L. We detected none in healthy individuals or in 50 patients with multiple sclerosis, 23 with dementia, or 20 with meningitis. S100 was detectable in serum of only a few patients with meningoradiculitis (2/20), peripheral neuropathy (2/30), encephalitis (1/14), Guillain-Barré syndrome (1/25), or AIDS (2/20). In contrast, we observed high concentrations in 29 of 75 patients with tumors of the central nervous system, especially in meningioma (6/9), glioblastoma (9/23), and neurinoma (5/5). Values for S100 were mainly abnormally high (greater than 0.3 microgram/L) in serum from patients with cerebrovascular disorders (43/48) or with metastases of melanoma (9/11).

Pregnancy-specific beta 1 glycoprotein (SP1) in the cerebrospinal fluid.

Pregnancy-specific beta 1 glycoprotein (SP1) was assayed by Particle Counting Assay in the cerebrospinal fluid (CSF) from 26 non-neurological patients, from 190 patients with various neurological disorders and from 84 patients with malignant hemopathies. With a sensitivity limit of 0.5 microgram/l, SP1 was undetectable in normal CSF. High levels were observed in CSF from one pregnant woman with herpetic encephalitis and from another woman with post-puerperal thrombophlebitis as a result of high serum concentrations and leakage of the blood-brain barrier. SP1 was detected at low levels in the CSF from 1 patient out of 5 with Creutzfeldt-Jakob disease and from a patient with Behçet's disease. Seven patients out of 84 with malignant hemopathies presented cerebral involvement; 3 of them had detectable SP1. However, SP1 was also detected in the CSF of 2 patients in apparently complete remission. The determination of SP1 in CSF appears to be of limited value in the diagnosis of neurological disorders and in the early detection of a cerebral localization of malignant hemopathies.

Pregnancy-specific beta 1-glycoprotein in serum in monoclonal gammopathies: relationship with serum beta 2-microglobulin, and cellular origin.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle-counting immunoassay in serum from 86 healthy blood donors and 236 patients with various types of gammopathy. A concentration of 1 microgram/L was taken as the upper normal limit. Abnormally high values were found in one of 10 patients with monoclonal gammopathy of undetermined significance, in 65% of 152 patients with multiple myeloma, in 84% of 64 patients with Waldenström's macroglobulinemia, and in seven of 10 patients with monoclonal gammopathies associated with other myeloproliferative disorders. In a study of 90 myeloma patients, the SP1 value correlated (p less than 0.001) with the concentration of beta 2-microglobulin in serum, a value which had been corrected for possible renal dysfunction, but not with the concentration of the monoclonal component. SP1 was detected by direct immunofluorescence in myeloma cells of bone-marrow smears from six of 10 patients with myelomatosis. These six patients had serum SP1 values greater than 1 microgram/L, whereas the four patients with fluorescence-negative myeloma cells had SP1 values less than 1 microgram/L.

Particle-counting immunoassay of a fetuin-like antigen in serum and cerebrospinal fluid.

A fetuin-like antigen was detected (smallest concentration detectable: 5 micrograms/L) by particle-counting immunoassay in 2% (13/641) of consecutive patients' sera but not in sera from 80 healthy blood donors, 40 neonates, or 40 pregnant women. The relation of the presence of detectable antigen to patients' diagnosis is not yet clear. However, in the group with cancer (154), it was found only in two of four patients with nephroblastoma and in three of five with tumors of tissue derived from the neurological crest: retinoblastoma (1/1), neuroblastoma (1/3), and medulloblastoma (1/1). Serum specimens from 422 patients with neurological disorders showed the antigen at a concentration greater than 5 micrograms/L in cases of neurosyphilis (5/11), peripheral neuropathy (12/38), Guillain-Barré syndrome (7/27), and multiple sclerosis (74/184). When we assayed 232 specimens of cerebrospinal fluid from the same neurological patients, we found the antigen in two cases of multiple sclerosis (6 and 15 micrograms/L) and in one case of Guillain-Barré syndrome (54 micrograms/L).

Prognostic value of concentration of pregnancy-specific beta 1-glycoprotein (SP1) in serum of patients with breast cancer.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle counting immunoassay in serum from 46 healthy female blood donors, 33 patients with benign mastopathy and 84 patients with breast cancer before operation and during follow-up. Values greater than 1 micrograms/1 were found more frequently with benign mastopathies (11/33) and in patients with breast cancer at stage 2 (20/48), 3 (4/9), and 4 (7/10) than in healthy female blood donors (3/46). The survival rate after 4 years was significantly lower in patients with SP1 level greater than 1 microgram/1 before tumor resection (52% vs. 87%). The difference remained significant when only patients in stage 2 were taken into account (57% vs. 85%). A highly significant (r = 0.64; N = 46) negative correlation was observed between the concentration of SP1 in serum and the concentration of estrogen receptor in the tumor. The longitudinal study of patients in stage 2 indicated that, of the 15 whose SP1 concentration fell below 1 microgram/1 after operation, 14 survived over 4 years whereas during the same period, 9 of the 10 patients whose SP1 value remained higher than 1 microgram/1 died.

Particle-counting immunoassay (PACIA) of pregnancy-specific beta 1-glycoprotein, a possible marker of various malignancies and Crohn's ileitis.

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle-counting immunoassay (PACIA) with a sensitivity of 1 microgram/L. In serum from 50 men, the SP1 concentration was less than 1 microgram/L, whereas three of the specimens from 46 nonpregnant women had values exceeding 1 microgram/L. In 29% of 950 consecutive patients' sera, SP1 concentrations exceeded 1 microgram/L--in sarcoma (six of six), in malignant hemopathies (101/127, 80%) such as myeloma (20/26, 92%) and acute myeloblastic leukemia (23/27, 90%), and in various other types of cancer (11/19, 58%) except for bronchial epithelioma, which did not lead to any significant increase of SP1 in the five patients examined. The concentration of SP1 was also frequently increased in patients with Crohn's ileitis (28/43, 65%) but not in patients with other inflammatory disorders.