IMPORTANCE Celiac disease is an autoimmune disorder triggered by gluten in genetically predisposed individuals. Gluten sensitivity can cause neurologic manifestations, such as ataxia or neuropathy, with or without gastrointestinal symptoms. Many patients with gluten ataxia produce antibodies toward the newly identified neuronal transglutaminase 6 (TG6). Two case reports described patients initially diagnosed with amyotrophic lateral sclerosis (ALS) and ultimately with celiac disease who improved with a strict gluten-free diet. OBJECTIVE To evaluate the prevalence of celiac disease-related antibodies and HLA antigen alleles, as well as TG6 antibodies, in patients with ALS and healthy individuals serving as controls to determine whether a neurologic presentation of a gluten-related disorder mimicking ALS might occur in some patients. DESIGN, SETTING, AND PARTICIPANTS In a case-control study conducted in an ALS tertiary center, we measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase 2 (TG2) and endomysium, as well as IgA and IgG antibodies to deamidated gliadine peptide and TG6 and performed HLA antigen genotyping in 150 consecutive patients with ALS and 115 healthy volunteers of similar age and sex. Participants did not have any known autoimmune or gastroenterologic disorder and were not receiving any immunomodulatory medications. The study was conducted from July 1, 2010, to December 31, 2012. MAIN OUTCOMES AND MEASURES Antibody levels and frequency of individuals with abnormal antibody values as well as frequency of HLA antigen alleles were compared between patient and control groups. RESULTS All patients and control group participants were seronegative to IgA antibodies to TG2, endomysium, and deamidated gliadine peptide. Twenty-three patients (15.3%) were seropositive to TG6 IgA antibodies as opposed to only 5 controls (4.3%) (P = .004). The patients seropositive for TG6 showed a classic picture of ALS, similar to that of seronegative patients. Fifty patients and 20 controls were tested for celiac disease-specific HLA antigen alleles; 13 of 22 TG6 IgA seropositive individuals (59.1%) were seropositive for celiac disease-related alleles compared with 8 (28.6%) of the 28 seronegative individuals (P = .04). Mean (SD) levels of IgA antibodies to TG2 were 1.78 (0.73) in patients and 1.58 (0.68) in controls (normal, <10). In a subset of study participants, mean levels of deamidated gliadin peptide autoantibodies were 7.46 (6.92) in patients and 6.08 (3.90) in controls (normal, <16). Mean levels of IgA antibodies to TG6 were 29.3 (30.1) in patients and 21.0 (27.4) in controls (P = .02; normal, <26). CONCLUSIONS AND RELEVANCE The data from this study indicate that, in certain cases, an ALS syndrome might be associated with autoimmunity and gluten sensitivity. Although the data are preliminary and need replication, gluten sensitivity is potentially treatable; therefore, this diagnostic challenge should not be overlooked.

Serum beta-2 microglobulin (B-2M) levels were studied in 365 breast cancer patients and 210 age-matched controls. The patients were divided into three groups: Group A, new patients at diagnosis; Group B, patients at follow-up; and Group C, metastatic patients. The mean B-2M of all breast cancer patients plus or minus one standard deviation (3.5 +/- 1.2; range, 1.1 to 5.9) was significantly higher than normal controls (1.29 +/- 0.49; range, 0.3 to 2.3; P less than 0.005). When the three patient groups were compared with each other, the mean B-2M level of Group A (3.0 +/- 1.5; range, 0.9 to 6.9) was similar to that of Group C (4.22 +/- 1.1; range, 2.0 to 6.4). The mean B-2M of both Groups A and C was significantly higher than that of Group B (2.38 +/- 1.02, range, 0.4 to 5.4; P less than 0.001). In Group A the mean B-2M decreased significantly after a 12-month period and reached the mean level of Group B but not that of normal controls. When patients in Group B were analyzed by their stage of disease at diagnosis, there was no significant difference between Stages I and II. There was a significant difference in the mean B-2M levels between Stages I and III. In relapsing patients, mean B-2M levels increased. These findings suggest that serum B-2M levels may reflect tumor burden, and even in patients at follow-up, occult tumor cells may activate the immune system.

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CD14, originally recognized as a lipopolysaccharide (LPS) receptor, has recently been implicated in the process of T-cell suppression and apoptosis. Its soluble form has been shown to bind, in vitro, to human T cells, a process that may carry a negative signal onto these cells. We recently described a novel lymphocyte population in human peripheral blood, a population that expresses an intracellular CD14-like antigen. This novel T-cell population, composed mainly of CD8 cells and of very few CD4 cells, was found to be greatly enhanced in asymptomatic, untreated human immunodeficiency virus (HIV)-positive individuals. In the present study, we further characterized this cell population and found that it differed from other CD8 subpopulations associated with HIV infection such as CD8/CD38. In addition, we followed HIV patients under conditions of highly active antiretroviral therapy (HAART) and observed two groups of patients: patients in whom the CD14-like positive-testing T cells returned to normal within 1 to 3 months, and patients in whom it did not, in spite of a significant plasma HIV-RNA viral load decrease. Thus, this new CD14-like positive-testing lymphocyte population may represent an interesting and important component of the cellular events associated with HIV infection. On the basis of its modulation following HAART, we speculate that it may be used, in the future, as a drug-monitoring cellular marker in antiretroviral treatment.CD14 is a 55-kDa glycosylphosphatidylinositol (GPI)-linked protein present on the surface membrane of phagocytic leukocytes. It is also present in a soluble form in serum. CD14 is one major molecule responsible for the innate host inflammatory response to microbial infection. As a key receptor for lipopolysaccharide (LPS) on the surface of monocytes and macrophages, the CD14 molecule was thought, until recently, to be involved primarily in nonspecific host defense mechanisms against gram-negative bacteria (2,6,10,19,20).A number of recently published results confer to this interesting molecule novel functions that are linked to apoptosis and also to T-cell activation. Thus, CD14 may function as an "apoptotic cell receptor" on the surface of phagocytes, since it seems to bind to phosphatidylserine which is externally exposed by apoptotic cells (1, 4); it may also be linked to susceptibility of monocytes or other cells to apoptosis, as it has been shown that a high level of expression of CD14 may protect cells from apoptosis and vice versa (11-13). Particularly interesting, CD14 either as a recombinant protein or as a native molecule secreted by monocytes in vitro has been recently shown to bind to the surface of in vitro-activated human T cells (7, 18). Most importantly, this binding was shown to convey a negative signal onto these T cells (16), in the form of interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-␥) inhibition, probably due to the inactivation of NF-B (18).These results have been reported from studies of cells cultured in vitro and artificially activated. We hav...

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