Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease of the central nervous system (CNS) with a high socioeconomic relevance. The pathophysiology of MS, which is both complex and incompletely understood, is believed to be influenced by various environmental determinants, including diet. Since the 1990s, a correlation between the consumption of bovine milk products and MS prevalence has been debated. Here, we show that C57BL/6 mice immunized with bovine casein developed severe spinal cord pathology, in particular, demyelination, which was associated with the deposition of immunoglobulin G. Furthermore, we observed binding of serum from casein-immunized mice to mouse oligodendrocytes in CNS tissue sections and in culture where casein-specific antibodies induced complement-dependent pathology. We subsequently identified myelin-associated glycoprotein (MAG) as a cross-reactive antigenic target. The results obtained from the mouse model were complemented by clinical data showing that serum samples from patients with MS contained significantly higher B cell and antibody reactivity to bovine casein than those from patients with other neurologic diseases. This reactivity correlated with the B cell response to a mixture of CNS antigens and could again be attributed to MAG reactivity. While we acknowledge disease heterogeneity among individuals with MS, we believe that consumption of cow's milk in a subset of patients with MS who have experienced a previous loss of tolerance to bovine casein may aggravate the disease. Our data suggest that patients with antibodies to bovine casein might benefit from restricting dairy products from their diet.

Long-term pulmonary function testing in pediatric bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

RATIONALE: Bronchiolitis obliterans syndrome (BOS) is a severe, chronic inflammation of the airways leading to an obstruction of the bronchioles. So far, there are only a few studies looking at the long-term development of pulmonary impairment in children with BOS. OBJECTIVE: The objective of this study was to investigate the incidence and long-term outcome of BOS in children who underwent allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Medical charts of 526 children undergoing HSCT in Frankfurt/Main, Germany between 2000 and 2017 were analyzed retrospectively and as a result, 14 patients with BOS were identified. A total of 271 lung functions (spirometry and body plethysmography), 26 lung clearance indices (LCI), and 46 chest high-resolution computed tomography (HRCT) of these 14 patients with BOS were evaluated. RESULTS: Fourteen patients suffered from BOS after HSCT (2.7%), whereby three distinctive patterns of lung function impairment were observed: three out of 14 patients showed a progressive lung function decline; two died and one received a lung transplant. In five out of 14 patients with BOS persisted with a severe obstructive and secondarily restrictive pattern in lung function (forced vital capacity [FVC] < 60%, forced expiratory volume in 1 second [FEV1] < 50%, and FEV1/FVC < 0.7) and increased LCI (11.67-20.9), six out of 14 patients recovered completely after moderate lung function impairment and signs of BOS on HRCT. Long-term FVC in absolute numbers was increased indicating that the children still have lung growth. CONCLUSION: Our results showed that the incidence of BOS in children is low. BOS was associated with high mortality and may lead to persistent obstructive lung disease; although, lung growth continued to exist.