Cause
The postulated cells of origin of T-LGLL leukemia are transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T-cell with clonal rearrangements of γ chain T-cell receptor genes for a minority of cases. Diagnosis
Laboratory findings
The requisite lymphocytosis of this disease is typically 2-20x109/L.Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen. Peripheral blood
The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as perforin and granzyme B. Flow cytometry is also commonly used. Bone marrow
Bone marrow involvement in this disease is often present, but to a variable extent. Bone marrow biopsy is commonly used for diagnosis. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs. Immunophenotype
The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell subset immunophenotype versus other permutations of those markers. Variable expression of CD11b, CD56, and CD57 are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive. Genetic findings
Clonal rearrangements of the T-cell receptor (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy. Treatment
First line treatment is immunosuppressive therapy.
Rates in the African meningitis belt were as high as 1 in 1,000 to 1 in 100 before introduction of a vaccine in 2010. The incidence of meningococcal disease is highest among infants (children younger than 1-year-old) whose immune system is relatively immature. In industrialized countries there is a second peak of incidence in young adults, who are congregating closely, living in dormitories or smoking. Vaccine development is ongoing.It is spread through saliva and other respiratory secretions during coughing, sneezing, kissing, and chewing on toys. Inhalation of respiratory droplets from a carrier which may be someone who is themselves in the early stages of disease can transmit the bacteria. Close contact with a carrier is the predominant risk factor. Other risk factors include a weakened general or local immune response, such as a recent upper respiratory infection, smoking, and complement deficiency. The incubation period is short, from 2 to 10 days. In susceptible individuals, N. meningitidis may invade the bloodstream and cause a systemic infection, sepsis, disseminated intravascular coagulation, breakdown of circulation, and septic shock. History
In 1884 Ettore Marchiafava and Angelo Celli first observed the bacterium inside cells in the cerebral spinal fluid (CSF). In 1887 Anton Weichselbaum isolated the bacterium from the CSF of patients with bacterial meningitis. He named the bacterium Diplococcus intracellularis meningitidis. Biotechnology
Components from Neisseria meningitidis are being harnessed in biotechnology. Its Cas9 enzyme is a useful tool in CRISPR gene editing because the enzyme is small and has distinct targeting features to the commonly used enzyme from Streptococcus pyogenes.