Autoantibody Profile of a Cohort of 78 Italian Patients with Mucous Membrane Pemphigoid: Correlation Between Reactivity Profile and Clinical Involvement.

Direct diagnosis of mucous membrane pemphigoid (MMP) is not easy. Circulating autoantibodies targeting bullous pemphigoid antigens of 180 kDa and 230 kDa (BP180 and BP230), α6ß4 integrin, laminin 332 and type VII collagen (Col VII) are not always present. The aims of this study were to characterize the humoral immune response of a cohort of Italian patients with MMP, its association with clinical involvement and severity, and to design an algorithm for efficient serological diagnosis. Seventy-eight MMP sera were studied retrospectively by indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Indirect immunofluorescence on salt-split skin resulted in the most sensitive approach for diagnosis of MMP. BP180 was the major autoantigen in MMP patients with oral and cutaneous involvement. Significant associations were found between BP180 reactivity and oral and cutaneous localization of the lesions (p = 0.006), and between Col VII positivity and Setterfield severity score (p = 0.020).

A clinically complex form of dominant optic atrophy (OPA8) maps on chromosome 16.

Dominant optic atrophy (DOA) is genetically heterogeneous and pathogenic mutations have been identified in the OPA1 and OPA3 genes, both encoding for mitochondrial proteins. We characterized clinical and laboratory features in a large OPA1-negative family with complicated DOA. Search for mitochondrial dysfunction was performed by studying muscle biopsies, fibroblasts, platelets and magnetic resonance (MR) spectroscopy. Genetic investigations included mitochondrial DNA (mtDNA) analysis, linkage analysis, copy number variation (CNV) analysis and candidate gene screening. Optic neuropathy was undistinguishable from that in OPA1-DOA and frequently associated with late-onset sensorineural hearing loss, increases of central conduction times at somato-sensory evoked potentials and various cardiac abnormalities. Serum lactic acid after exercise, platelet respiratory complex activities, adenosine triphosphate (ATP) content in fibroblasts and muscle phosphorus MR spectroscopy all failed to reveal a mitochondrial dysfunction. However, muscle biopsies and their mtDNA analysis showed increased mitochondrial biogenesis. Furthermore, patient's fibroblasts grown in the galactose medium were unable to increase ATP content compared with controls, and exhibited abnormally high rate of fusion activity. Genome-wide linkage revealed a locus on chromosome 16q21-q22 with a maximum two-point LOD score of 8.84 for the marker D16S752 and a non-recombinant interval of ∼ 6.96 cM. Genomic screening of 45 genes in this interval including several likely candidate genes (CALB2, CYB5B, TK2, DHODH, PLEKHG4) revealed no mutation. Moreover, we excluded the presence of CNVs using array-based comparative genome hybridization. The identification of a new OPA locus (OPA8) in this pedigree demonstrates further genetic heterogeneity in DOA, and our results indicate that the pathogenesis may still involve mitochondria.

Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy.

PURPOSE: To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (StratusOCT) in patients with Leber's hereditary optic neuropathy (LHON). DESIGN: Cross-sectional study. PARTICIPANTS AND/OR CONTROLS: Thirty-eight patients with LHON were analyzed and compared with an age-matched control group of 75 patients. Patients with LHON were classified as having early LHON (E-LHON, n = 8) when the duration of the disease was shorter than 6 months and atrophic LHON (A-LHON, n = 30) when the duration was longer than 6 months. METHODS: The fast RNFL thickness (3.4) scan acquisition protocol was used. MAIN OUTCOME MEASURE: Retinal nerve fiber layer thickness as measured by StratusOCT. RESULTS: Compared with the control group, eyes with E-LHON showed a thicker RNFL in the 360 degrees average measurement (P<0.01) and in the superior (P<0.01), nasal (P<0.05), and inferior quadrants (P<0.05); no significant changes were detected in the temporal quadrant. Eyes with A-LHON revealed a thinner RNFL in all measurements (P<0.001); the fibers of the nasal quadrant showed the lowest amount of reduction (38% vs. 42%-49.8% in the other quadrants). In cases with A-LHON and visual recovery, RNFL was significantly thicker in all measurements (P<0.001), except the temporal quadrant, with respect to A-LHON without visual recovery. CONCLUSIONS: On the basis of OCT data, the RNFL is thickened in E-LHON and severely thinned in A-LHON. RNFL is likely to be partially preserved in A-LHON with visual recovery. The temporal fibers (papillomacular bundle) are the first and most severely affected; the nasal fibers seem to be partially spared in the late stage of the disease.

Retinal nerve fiber layer evaluation by optical coherence tomography in unaffected carriers with Leber's hereditary optic neuropathy mutations.

PURPOSE: To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in unaffected carriers with Leber's hereditary optic neuropathy (LHON) mutations. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-six unaffected carriers (44 females and 22 males) were analyzed and compared with an age-matched control group of 70 patients (40 females and 30 males). The statistical analysis was performed after grouping both the patients and the control group on the basis of gender and, for unaffected carriers only, mitochondrial DNA mutation. METHODS: The Fast RNFL Thickness (3.4) scan acquisition protocol was used. MAIN OUTCOME MEASURE: Retinal nerve fiber layer thickness as measured by OCT. RESULTS: With respect to the control group, unaffected male carriers showed a thicker RNFL in the temporal and inferior quadrants and in the 360 degrees average measurement (P = 0.025, P = 0.03, and P = 0.018, respectively). These differences reached statistical significance in subjects carrying the 11778 mutation, whereas only a trend was detected in those with the 3460 mutation. Unaffected female carriers had an increased thickness in the temporal quadrant when compared with the control group (P = 0.003) and no differences in the other measurements. The increase in temporal sectors was statistically significant in females with the 11778 mutation, whereas a trend was detected in those with the 3460 mutation. CONCLUSIONS: A thickening of the temporal fibers was detected in all subgroups of unaffected carriers. This is the first evidence indicating the preferential involvement of the papillomacular bundle in subclinical LHON. This notion previously was based on the early loss of fibers from the temporal quadrant in acute LHON and the selective loss of small-caliber fibers at histopathology. Our study also revealed that males have a more diffuse involvement than females.

Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.

Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin-related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in six patients from two unrelated families carrying the c.2708-2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate production rate, was significantly delayed in the patients. Our in vivo results show for the first time to our knowledge a deficit of oxidative phosphorylation in OPA1-related DOA.

Comparison of deep sclerectomy with implant and combined glaucoma surgery.

To evaluate the efficacy of combined glaucoma surgery, 42 glaucomatous patients were randomly divided into two groups: deep sclerectomy with implant (DS) alone was performed in 21 patients, and combined deep sclerectomy and phacoemulsification (PDS) was performed in the other 21 patients. Follow-up was carried out at regular intervals for 12 months. A comparative study on intraocular pressure (IOP) was designed. Although further study is needed, PDS appears to have better postoperative long-term results in IOP control than DS alone.